KURIYAMA HIROSHI (JP)
SHODA MOTOSHI (JP)
KURIYAMA HIROSHI (JP)
| WO1993012095A1 | 1993-06-24 | |||
| WO1996032379A1 | 1996-10-17 | |||
| WO2002028853A1 | 2002-04-11 | |||
| WO2001039773A1 | 2001-06-07 | |||
| WO2003070686A1 | 2003-08-28 |
| GB1379526A | 1975-01-02 | |||
| DE2046992A1 | 1972-03-30 | |||
| JPS396668B1 | ||||
| JPS5058087A | 1975-05-20 |
See also references of EP 1660427A4
| 1. | A compound represented by the formula (I): [In the formula, Link represents a saturated or unsaturated straight hydrocarbon chain having 1 to 3 carbon atoms. C2, C3, C4, C5, and C6 in the aromatic ring (E) independently represent a ringconstituting carbon atom. One of the ringconstituting carbon atoms to which Rs and AR do not bind may be replaced with V. V represents nitrogen atom, or carbon atom substituted with Zx. Zx represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, nitro group, OR9, orN (Rnl) (Rn2). R9 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, orAs Qp, wherein A6 represents a single bond or methylene, Qp represents phenyl group, and the phenyl group may be substituted with one of T'or two or more of the same or different Tl. T'represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, hydroxyl group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, nitro group, an alkoxy group having 1 to 4 carbon atoms, or a monoor dialkylamino group having 1 to 4 carbon atoms. Rnl represents hydrogen atom or a linear or branched saturated alkyl group having 1 to 4 carbon atoms, Rn2 has the same meaning as Rnl, or representsCOR23 orSO2R24, or binds to Rnl to form a 3to 6membered ring together with the nitrogen atom to which they bind to form a saturated nitrogencontaining cycloalkyl group or morpholino group. R23 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms,OA6Qp, orN (R25) (R26). R25 represents hydrogen atom, or a linear or branched saturated alkyl group having 1 to 4 carbon atoms. R26 has the same meaning as R25, or binds to R25 to form a 3 to 6membered ring together with the nitrogen atom to which they bind to form a saturated nitrogencontaining cycloalkyl group or morpholino group. R24 represents a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono or dialkylamino group having 1 to 4 carbon atoms. Rs representsDRx orN (Ry) (Rz). D represents a single bond, oxygen atom, sulfur atom,S (O),S (O) 2, or C (O). Rx represents a linear or branched saturated alkyl group having 3 to 8 carbon atoms, Ra represented by the following formula: Ri (CH2) k (Ra) Rb represented by the following formula : (Rb) or Rc represented by the following formula. Symbol k in Ra represents 0 or an integer of 1 to 3. R1 represents a saturated cyclic alkyl group having 3 to 7 carbon atoms, or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms, and Rl may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms. Q in Rb represents a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or a heterocyclic ring (q), and binds to A2 at an arbitrary position on the ring. The heterocyclic ring (q) contains the same or different 1 to 4 ringconstituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. A1 represents a single bond or an alkylene (a) having 1 to 3 carbon atoms, and the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group. A2 represents a single bond, oxygen atom, sulfur atom,S (O),S (0) 2, orN (R4) (provided that when A2 represents oxygen atom, sulfur atom,S (O),S (0) 2 orN (R4) , Al represents ethylene or trimethylene). R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,OR5,N (R6) (R6'),NHCOR, NHSO2R3, orA6Qa, or they bind to each other to represent methylenedioxy group. Qa represents a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or a heterocyclic ring (qa), binds to A6 at an arbitrary position on the ring, and may be substituted with one of T1 or two or more of the same or different T1. The heterocyclic ring (qa) contains the same or different 1 to 4 ringconstituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. R5 and R7 independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, orA6Qa. R3 represents a lower alkyl group having 1 to 4 carbon atoms. R6'has the same meaning as R6, or binds to R6 to form a 3to 6membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogencontaining cycloalkyl group or morpholino group. Symbol p in Rc represents an integer of 2 to 4. A4 represents a single bond, methylene, or ethylene. A5 representsC (O),C (S), orS (0) 2. Rd represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa. Re represents an alkyl group having 1 to 8 carbon atoms,A6Qa, (CH2) iRl4,OR28,SR28, orN (R29) (R30). Symbol i represents an integer of 1 to 3, R14 represents hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N dialkylcarbamoyl group having 1 to 4 carbon atoms. R28 represents an alkyl group having 1 to 8 carbon atoms, orA6Qa. R29 represents an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, orAsQa. R30 represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3to 6membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogencontaining cycloalkyl group or morpholino group. Rz has the same meaning as Rx, or Rz represents methyl group, ethyl group, orA5Re. Ry represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, orA6Qp, or Ry may bind to Rz to form, together with a nitrogen atom to which they bind, a saturated or unsaturated 3 to 7membered nitrogencontaining cyclic group, wherein said nitrogencontaining cyclic group may optionally be substituted with one or two lower alkyl groups having 1 to 4 carbon atoms wherein said two alkyl groups may be the same or different. AR represents a partially unsaturated or completely unsaturated condensed bicyclic carbon ring or a heterocyclic ring (ar), and may be substituted with one of Xa or two or more of the same or different Xa. The heterocyclic ring (ar) contains the same or different 1 to 4 ringconstituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. Xa represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, a saturated cyclic alkyl group having 3 to 7 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group,(CH2) iRl4,ORl°,N (Rll) (Rl2), SO2Rl3, orCOR27. Rio represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or(CH2) iRJ4. Rll represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. R12 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms, CORl5, orSO2Rl6, or binds to R"to form a 3to 6membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogencontaining cycloalkyl group or morpholino group. R15 represents a lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms, amino group, a monoor dialkylamino group having 1 to 4 carbon atoms, orA6Qa. R13 and R16 independently represent a lower alkyl group having 1 to 4 carbon atoms, amino group, or a monoor dialkylamino group having 1 to 4 carbon atoms. R27 represents hydrogen atom, hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, a lower alkyl group having 1 to 4 carbon atoms, amino group, or a monoor dialkylamino group having 1 to 4 carbon atoms. Y represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, (CH2) mN (R18) (Ri9) orC (R20) 20C (O) A3R21. Symbol m represents an integer of 2 or 3. R18 is the same as Rl9, or binds to Rl9 to form a 3to 6membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogencontaining cycloalkyl group or morpholino group. Rl9 represents methyl group, ethyl group, or propyl group. R20 represents hydrogen atom, methyl group, ethyl group, or propyl group. R2l represents a lower alkyl group having 1 to 4 carbon atoms, a cyclic saturated alkyl group having 3 to 6 carbon atoms, or phenyl group, and A3 represents a single bond, or oxygen atom. ] or a salt thereof. |
| 2. | The compound or salt thereof according to claim 1, wherein Link is (CH2) n, n is an integer of 1 to 3, Rz has the same meaning as that of Rx or representsA5Re when Rs isN (Ry) (Rz), and Ry is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or A6Qp, or Ry binds to Rz to form, together with a nitrogen atom to which they bind, a saturated or unsaturated 3 to 7membered nitrogencontaining cyclic group. |
| 3. | The compound or salt thereof according to claim 2, wherein AR is a residue of naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro3Hbenzothiazole, quinoline, dihydrolHquinoline, benzo [d] isothiazole, 1Hindazole, benzo [c] isothiazole, 2Hindazole, imidazo [1, 2a] pyridine, 1H pyrrolo [2, 3b] pyridine, isoquinoline, dihydro2Hisoquinoline, cinnoline, quinazoline, quinoxaline, lHbenzimidazole, benzoxazole, 1Hpyrrolo [3, 2b] pyridine, benzo [1, 2,5] thiadiazole, 1Hbenzotriazole, 1, 3dihydropyrrolo [2, 3b] pyridine, 1,3 dihydrobenzimidazole, dihydro3Hbenzoxazole, phthalazine, [1, 8] naphthalidine, [1, 5] naphthalidine, lHpyrrolo [3, 2c]pyridine, 1Hpyrrolo [2, 3e] pyridine, 1H pyrazolo [4, 3b]pyridine, 1Hpyrazolo [4, 3c] pyridine, lHpyrazolo [3, 4c] pyridine, 1H pyrazolo [3, 4b] pyridine, [1, 2,4] triazolo [4, 3a]pyridine, thieno [3, 2c] pyridine, thieno [3, 2b]pyridine, 1Hthieno [3, 2c] pyrazole, benzo [d] isoxazole, benzo [c] isoxazole, indolizine, 1,3dihydroindole, lHpyrazolo [3, 4d] thiazole, 2H isoindole, [1, 2,4] triazolo [1, 5a]pyrimidine, 1Hpyrazolo [3, 4b] pyrazine, 1H imidazo [4, 5b] pyrazine, 7Hpurine, or 4Hchromene (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa). |
| 4. | The compound or salt thereof according to claim 2, wherein AR is naphthalen2yl group, naphthalen1yl group, benzofuran5yl group, benzofuran 4yl group, benzofuran2yl group, benzo [b] thiophen5yl group, benzo [b] thiophen4 yl group, benzo [b] thiophen2yl group, indol5yl group, indol4yl group, indol6yl group, benzothiazol6yl group, benzothiazol7yl group, benzothiazol5yl group, benzothiazol4yl group, dihydro3Hbenzothiazol6yl group, dihydro3H benzothiazol7yl group, dihydro3Hbenzothiazol5yl group, dihydro3H benzothiazol4yl group, quinolin6yl group, quinolin3yl group, quinolin5yl group, quinolin7yl group, dihydrolHquinolin6yl group, dihydrolHquinolin5 yl group, benzo [d] isothiazol5yl group, benzo [d] isothiazol4yl group, benzo [d] isothiazol6yl group, benzo [d] isothiazol7yl group, lHindazol5yl group, lHindazol4ylgroup, lHindazol6yl group, benzo [c] isothiazol5yl group, benzo [c]isothiazol4yl group, benzo [c]isothiazol6yl group, benzo [c] isothiazol7yl group, 2Hindazol5yl group, 2Hindazol4yl group, 2Hindazol6yl group, imidazo [1, 2a]pyridin6yl group, imidazo [1, 2a]pyridin7yl group, lHpyrrolo [2,3 b]pyridin5yl group, 1Hpyrrolo [2, 3b] pyridin4yl group, isoquinolin6yl group, isoquinolin3yl group, isoquinolin5yl group, isoquinolin7yl group, dihydro2H isoquinolin6yl group, dihydro2Hisoquinolin5yl group, cinnolin6yl group, cinnolin5yl group, quinazolin6yl group, quinazolin7yl group, quinazolin5yl group, quinoxalin2yl group, quinoxalin6yl group, quinoxalin5yl group, 1H benzimidazol5yl group, lHbenzimidazol4ylgroup, benzoxazol5yl group, benzoxazol6yl group, benzoxazol4yl group, benzoxazol7yl group, 1H pyrrolo [3, 2b] pyridin5yl group, 1Hpyrrolo [3, 2b]pyridin6yl group, benzol, 2,5] thiadiazol5yl group, benzo [1, 2,5] thiadiazol4yl group, 1H benzotriazol5yl group, lHbenzotriazol4yl group, 1, 3dihydropyrrolo [2, 3 b]pyridin5yl group, 1, 3dihydropyrrolo [2, 3b] pyridin4yl group, 1, 3 dihydrobenzimidazol5yl group, 1, 3dihydrobenzimidazol4yl group, dihydro3H benzoxazol6yl group, dihydro3Hbenzoxazol7yl group, dihydro3Hbenzoxazol5 yl group, dihydro3Hbenzoxazol4yl group, phthalazin6yl group, phthalazin5yl group, [1, 8] naphthalidin3yl group, [1, 8] naphthalidin4yl group, [1, 5] naphthalidin3yl group, [1, 5] naphthalidin4yl group, lHpyrrolo [3,2 c] pyridin6yl group, lHpyrrolo [3, 2c] pyridin4yl group, 1Hpyrrolo [2, 3c] pyridin 5yl group, 1Hpyrrolo [2, 3c] pyridin4yl group, 1Hpyrazolo [4, 3b] pyridin5yl group, 1Hpyrazolo [4, 3b] pyridin6yl group, 1Hpyrazolo [4, 3c] pyridin6yl group, 1Hpyrazolo [4, 3c] pyridin4yl group, 1Hpyrazolo [3, 4c] pyridin5yl group, 1H pyrazolo [3, 4c] pyridin4yl group, 1Hpyrazolo [3, 4b]pyridin5yl group, 1H pyrazolo [3, 4b] pyridin4yl group, [1, 2,4] triazolo [4, 3a] pyridin6yl group, [1, 2,4] triazolo [4, 3a] pyridin7yl group, thieno [3, 2c] pyridin2yl group, thieno [3,2 c] pyridin3yl group, thieno [3, 2c] pyridin6yl group, thieno [3, 2b] pyridin2yl group, thieno [3, 2b] pyridin3yl group, thieno [3, 2b] pyridin5yl group, thieno [3,2 b] pyridin6yl group, 1Hthieno [3, 2c] pyrazol5yl group, 1Hthieno [3, 2c] pyrazol4 yl group, benzo [d] isoxazol5yl group, benzo [d] isoxazol4yl group, benzo [d] isoxazol 6yl group, benzo [d] isoxazol7yl group, benzo [c] isoxazol5yl group, benzo [c] isoxazol4yl group, benzo [c] isoxazol6yl group, benzo [c] isoxazol7yl group, indolizin7yl group, indolizin6yl group, indolizine8yl group, 1, 3dihydroindol5 yl group, 1, 3dihydroindol4yl group, 1, 3dihydroindol6yl group, 1Hpyrazolo [3,4 d] thiazol5yl group, 2Hisoindol5yl group, 2Hisoindol4yl group, [1, 2,4] triazolo [1, 5a] pyrimidin6yl group, 1Hpyrazolo [3, 4b] pyrazin5yl group, 1Himidazo [4, 5b] pyrazin5yl group, 7Hpurin2yl group, 4Hchromen6yl group, or 4Hchromen5yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa). |
| 5. | The compound or salt thereof according to any one of claims 2 to 4 mentioned above, wherein Rs isDRx orN (Ry) (Rz), D is a single bond, oxygen atom, sulfur atom,S (O),S (0) 2, orC (O), Rx is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, RI is a saturated cycloalkyl group having 3 to 7 carbon atoms or a condensed saturated cycloalkyl group having 6 to 8 carbon atoms, Rl may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, 4Hchromenyl group, dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group, 1, 3dihydrobenzimidazole group, dihydro3Hbenzoxazole group, or dihydro3Hbenzothiazole group (the aforementioned groups bond to A2 at an arbitrary position on the rings), Al is a single bond or an alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group, A2 is a single bond, oxygen atom, sulfur atom,S (O),S (0) 2, orN (R4) (provided that when A2 represents oxygen atom, sulfur atom,S (O) ,S (0) 2, orN (R4), Al represents ethylene or trimethylene), R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,OR5,N (R6) (R6'),NHCOR7,NHSO2R8, orA6Qa, or they bind to each other to represent methylenedioxy group, Qa is phenyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, or indazolyl group (the aforementioned groups may be substituted with one of T1 or two or more of the same or different Tl, and bind to As at an arbitrary position on the rings), R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R5 and R7 independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, orA6Qa, R8 is a lower alkyl group having 1 to 4 carbon atoms, R6' has the same meaning as R6, or binds to R6 to form a 3to 6membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen containing cycloalkyl group or morpholino group, p in Rc is an integer of 2 to 4, A4 is a single bond or methylene or ethylene, A5 isC (O),C (S) , orS (0) 2, Rd is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa, Re is an alkyl group having 1 to 8 carbon atoms,A6Qa, (CH2) iRl4,OR28,SR28, orN (R29) (R30), i is an integer of 1 to 3, R14 is hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, Ndialkylcarbamoyl group having 1 to 4 carbon atoms, R28 is an alkyl group having 1 to 8 carbon atoms orA6Qa, R29 is an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, orA6Qa group, R30 is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3to 6membered ring together with the nitrogen atom to which they bind to form a saturated nitrogencontaining cycloalkyl group or morpholino group, Rz has the same meaning as Rx, or isA5Re, and Ry is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, orA6Qp, or binds to Rz to form a saturated or unsaturated nitrogencontaining cyclic substituent having 3 to 7 atoms together with nitrogen atom to which they binds. |
| 6. | The compound or salt thereof according to any one of claims 2 to 5, wherein Rs isORx. |
| 7. | The compound or salt thereof according to claim 2, wherein AR binds to C3 in the aromatic ring (E), and Rs binds to one of the ringconstituting carbon atoms C4, C5, and C6. |
| 8. | The compound or salt thereof according to claim 2, wherein AR binds to C2 in the aromatic ring (E), and Rs binds to one of the ringconstituting carbon atoms C3, C4, and C5. |
| 9. | The compound or salt thereof according to claim 7, wherein Rs is0Rx, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V. |
| 10. | The compound or salt thereof according to claim 8, wherein n is an integer of 2, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. |
| 11. | The compound or salt thereof according to claim 7, wherein Rs binds to the ringconstituting carbon atom C5 or C6 in the aromatic ring (E). |
| 12. | The compound or salt thereof according to claim 11, wherein Rs isORx, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V. |
| 13. | The compound or salt thereof according to claim 12, wherein n is an integer of 2, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. |
| 14. | The compound or salt thereof according to claim 7, wherein Rs binds to C4 in the aromatic ring (E), and C6 is replaced with V. |
| 15. | The compound or salt thereof according to claim 14, wherein n is an integer of 2, V is carbon atom substituted with Zx, D is oxygen atom, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. |
| 16. | The compound or salt thereof according to claim 7, wherein Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, and C2 and C6 are unsubstituted ringconstituting carbon atoms. |
| 17. | The compound or salt thereof according to claim 16, wherein n is an integer of 2, Rs isORx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. |
| 18. | The compound or salt thereof according to claim 7, wherein Rs binds to C4 in the aromatic ring (E), C5 is a ringconstituting carbon atom substituted with Zx, or an unsubstituted ringconstituting carbon atom, C2 and C6 are unsubstituted ringconstituting carbon atoms, and Rs isN (Ry) (Rz). |
| 19. | The compound or salt thereof according to claim 1, wherein Link is (CH2) n, n is an integer of 1 to 3, C2 and C6 in the aromatic ring (E) are unsubstituted ringconstituting carbon atoms, AR binds to C3 in the aromatic ring (E), and Rs isN (Ry) (Rz) and binds to C4 in the aromatic ring (E). |
| 20. | The compound or salt thereof according to claim 19, wherein n is 2, and C5 is carbon atom substituted with Zx or unsubstituted ringconstituting carbon atom. |
| 21. | The compound or salt thereof according to claim 19 or 20, wherein AR is naphthalen2yl group, naphthalen1yl group, benzofuran5yl group, benzofuran 4yl group, benzofuran2yl group, benzo [b] thiophen5yl group, benzo [b] thiophen4 yl group, benzo [b] thiophen2yl group, indol5yl group, indol4yl group, indol6yl group, benzothiazol6yl group, benzothiazol7yl group, benzothiazol5yl group, benzothiazol4yl group, dihydro3Hbenzothiazol6yl group, dihydro3H benzothiazol7yl group, dihydro3Hbenzothiazol5yl group, dihydro3H benzothiazol4yl group, quinolin6yl group, quinolin3yl group, quinolin5yl group, quinolin7yl group, dihydrolHquinolin6yl group, dihydrolHquinolin5 yl group, benzo [d] isothiazol5yl group, benzo [d] isothiazol4yl group, benzo [d] isothiazol6yl group, benzo [d] isothiazol7yl group, lHindazol5yl group, lHindazol4yl group, 1Hindazol6yl group, benzo [c] isothiazol5yl group, benzo [c] isothiazol4yl group, benzo [c] isothiazol6yl group, benzo [c] isothiazol7yl group, 2Hindazol5yl group, 2Hindazol4yl group, 2Hindazol6yl group, imidazo [1, 2a] pyridin6yl group, imidazo [1, 2a] pyridin7yl group, lHpyrrolo [2,3 b] pyridin5yl group, lHpyrrolo [2, 3bpyridin4yl group, isoquinolin6yl group, isoquinolin3yl group, isoquinolin5yl group, isoquinolin7yl group, dihydro2H isoquinolin6yl group, dihydro2Hisoquinolin5yl group, cinnolin6yl group, cinnolin5yl group, quinazolin6yl group, quinazolin7yl group, quinazolin5yl group, quinoxalin2yl group, quinoxalin6yl group, quinoxalin5yl group, 1H benzimidazol5yl group, lHbenzimidazol4yl group, benzoxazol5yl group, benzoxazol6yl group, benzoxazol4yl group, benzoxazol7yl group, 1H pyrrolo [3, 2b] pyridin5yl group, lHpyrrolo [3, 2b] pyridin6yl group, benzo [1, 2, 5] thiadiazol5yl group, benzo [1, 2,5] thiadiazol4yl group, 1H benzotriazol5yl group, lHbenzotriazol4yl group, 1, 3dihydropyrrolo [2,3 b] pyridin5yl group, 1, 3dihydropyrrolo [2, 3b] pyridin4yl group, 1,3 dihydrobenzimidazol5yl group, 1, 3dihydrobenzimidazol4yl group, dihydro3H benzoxazol6yl group, dihydro3Hbenzoxazol7yl group, dihydro3Hbenzoxazol5 yl group, dihydro3Hbenzoxazol4yl group, phthalazin6yl group, phthalazin5yl group, [1, 8] naphthalidin3yl group, [1, 8] naphthalidin4yl group, [1, 5] naphthalidin3yl group, [1, 5] naphthalidin4yl group, 1Hpyrrolo [3,2 c] pyridin6yl group, lHpyrrolo [3, 2c] pyridin4yl group, lHpyrrolo [2, 3c] pyridin 5yl group, 1Hpyrrolo [2, 3c]pyridin4yl group, 1Hpyrazolo [4, 3b] pyridin5yl group, 1Hpyrazolo [4, 3b] pyridin6yl group, lHpyrazolo [4, 3c] pyridin6yl group, 1Hpyrazolo [4, 3c] pyridin4yl group, 1Hpyrazolo [3, 4c] pyridin5yl group, 1H pyrazolo [3, 4c]pyridin4yl group, 1Hpyrazolo [3, 4b] pyridin5yl group, 1H pyrazolo [3, 4b] pyridin4yl group, [1, 2,4] triazolo [4, 3a] pyridin6yl group, [1, 2,4] triazolo [4, 3a]pyridin7yl group, thieno [3, 2c] pyridin2yl group, thieno [3, 2 c]pyridin3yl group, thieno [3, 2c] pyridin6yl group, thieno [3, 2b]pyridin2yl group, thieno [3, 2b] pyridin3yl group, thieno [3, 2b] pyridin5yl group, thieno [3,2 b] pyridin6yl group, lHthieno [3, 2c] pyrazol5yl group, lHthieno [3, 2c] pyrazol4 yl group, benzo [d]isoxazol5yl group, benzo [d]isoxazol4yl group, benzo [d] isoxazol 6yl group, benzo [d]isoxazol7yl group, benzo [clisoxazol5yl group, benzo [c]isoxazol4yl group, benzo [c]isoxazol6yl group, benzo [c] isoxazol7yl group, indolizin7yl group, indolizin6yl group, indolizine8yl group, 1, 3dihydroindol5 yl group, 1, 3dihydroindol4yl group, 1, 3dihydroindol6yl group, 1Hpyrazolo [3, 4 d] thiazol5yl group, 2Hisoindol5yl group, 2Hisoindol4yl group, [1, 2,4] triazolo [1, 5a] pyrimidin6yl group, 1Hpyrazolo [3, 4b] pyrazin5yl group, 1Himidazo [4, 5b]pyrazin5yl group, 7Hpurin2yl group, 4Hchromen6yl group, or 4Hchromen5yl group, wherein these groups may be substituted with one of Xa or two or more of the same or different Xa. |
| 22. | The compound or salt thereof according to any one of claim 19 to 21, wherein Rz is a linear or branched saturated alkyl group having 1 to 8 carbon atoms, or Rz is Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, Rl is a saturated cyclic alkyl group having 3 to 7 carbon atoms or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms, R1 may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, 4Hchromenyl group, dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group, 1, 3dihydrobenzimidazole group, dihydro3Hbenzoxazole group, or dihydro3Hbenzothiazole group (the aforementioned groups binds to A2 at an arbitrary position), Al is a single bond or an alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group, A2 is a single bond, oxygen atom, sulfur atom,S (O),S (0) 2, orN (R4) (provided that when A2 represents oxygen atom, sulfur atom,S (O),S (0) 2, orN (R4), A1 represents ethylene or trimethylene), R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, OR5,N (R6) (R6'),NHCOR7,NHS02Rs, orA6Qa, or they bind to each other to represent methylenedioxy group, Qa is phenyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, or indazolyl group (these groups may be substituted with one of T1 or two or more of the same or different T1, and bind to A6 at an arbitrary position on the ring), R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R5 and R7 independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, orA6Qa, R8 is a lower alkyl group having 1 to 4 carbon atoms, R6'has the same meaning as R6, or binds to R6 to form a 3to 6membered ring together with the nitrogen atom to which they bind to form a saturated nitrogencontaining cycloalkyl group or morpholino group, p in Rc is an integer of 2 to 4, A4 is a single bond or methylene or ethylene, A5 isC (O),C (S), orS (0) 2, Rd is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa, Re is an alkyl group having 1 to 8 carbon atoms,A6Qa, (CH2) iRl4,OR23,SR23, orN (R29) (R30), i is an integer of 1 to 3, R14 is hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N dialkylcarbamoyl group having 1 to 4 carbon atoms, R23 is an alkyl group having 1 to 8 carbon atoms orA6Qa, R29 is an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, orA6Qa group, R30 is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3 to 6membered ring together with the nitrogen atom to which they bind to form a saturated nitrogencontaining cycloalkyl group or morpholino group, and Ry is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or binds to Rz to form a saturated or unsaturated nitrogencontaining cyclic substituent having 3 to 7 atoms together with nitrogen atom to which they binds and said nitrogencontaining cyclic substituent may be substituted with one or two lower alkyl groups having 1 to 4 carbon atoms wherein said two alkyl groups may be the same or different. |
| 23. | The compound or salt thereof according to claim 7, wherein Rs binds to C4 in the aromatic ring (E), C5 is a ringconstituting carbon atom substituted with Zx, or an unsubstituted ringconstituting carbon atom, C2 and C6 are unsubstituted ringconstituting carbon atoms, Rs isDRx, and D is a single bond, sulfur atom, S (O),S (0) 2, orC (O). |
| 24. | The compound or salt thereof according to claim 7, wherein n is an integer of 2, Rs binds to C4 in the aromatic ring (E), C5 is carbon atom substituted withN (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2 and C6 are unsubstituted ringconstituting carbon atoms, Rs is ORx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. |
| 25. | The compound or salt thereof according to claim 7, wherein n is an integer of 2, Rs binds to C4 in the aromatic ring (E), C5 is a ringconstituting carbon atom substituted with the substituent Zx, or an unsubstituted ringconstituting carbon atom, C2 and C6 are unsubstituted ringconstituting carbon atoms, Rs isO Rc, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. |
| 26. | A medicament containing the compound according to any one of claims 1 to 25 or a pharmacologically acceptable salt thereof as an active ingredient. |
| 27. | An agent for suppressing production of a prostaglandin and/or leukotriene, which comprises the compound according to any one of claims 1 to 25 or a pharmacologically acceptable salt thereof as an active ingredient. |
| 28. | The medicament according to claim 26, which is for prophylactic and/or therapeutic treatment of a disease caused by production of a prostaglandin and/or leukotriene. |
| 29. | A compound represented by the formula (II) : [In the formula, C2', C3', C4', C5', and C6'in the aromatic ring (E') independently represent a ringconstituting carbon atom, any one of them to which Rs'and G do not bind may be replaced with V, V'represents nitrogen atom, or carbon atom substituted with Zx', Zx'has the same meaning as Zx mentioned above, provided that when Zx contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx contains amino group, the amino group may be protected with Rp2, Rs'representsDRx'orN (Ry') (Rz'), DRx'andN (Ry') (Rz') have the same meanings asDRx andN (Ry) (Rz) mentioned above, respectively, provided that whenDRx orN (Ry) (Rz) contains hydroxyl group, the hydroxyl group may be protected with Rpl, and whenDRx or N (Ry) (Rz) contains amino group, the amino group may be protected with Rp2, G represents chlorine atom, bromine atom, iodine atom, mesylate group, triflate group, or an arenesulfonate group of which aromatic portion may be substituted with one of T1 or two or more of the same or different Tl, and Y'represents a lower alkyl group having 1 to 4 carbon atoms]. |
| 30. | A compound represented by the formula (III) : [In the formula, C2', C3', C4', C5'and C6'in the aromatic ring (E') independently represent a ringconstituting carbon atom, any one of these ringconstituting carbon atoms to which Rs'and AR'do not bind may be replaced with V', and AR'has the same meaning as that of AR, provided that when AR contains hydroxyl group, the hydroxyl group may be protected with Rp, and whenAR contains amino group, the amino group may be protected with Rp2.]. |
Background Art Various kinds of prostaglandins and various kinds of leukotrienes are produced in the bodies of mammals in response to variety of stimuli such as inflammatory stimuli and physical stimuli.
Both of prostaglandins and leukotrienes are metabolites of arachidonic acid, and they are physiologically active substances referred to as lipid mediators, and they cause various physiological responses of mammals by binding to receptors expressed on surfaces of various cells or in the cells.
Arachidonic acid is produced from a phospholipid as a substrate, such as phosphatidylcholine which is a cell membrane component, with the aid of an enzymatic activity of phospholipase A2 (PLA2).
Arachidonic acid produced by the action of PLA2 is converted into prostaglandin (PG) H2 with the aid of an enzymatic activity of constitutive type cyclooxygenase (COX) 1 or inducible type COX-2, and further converted into PGE2, PGD2, PGF2 a, PGI2, thromboxane (TX) A2 and the like with the aid of each synthetic enzyme. Further, arachidonic acid is also metabolized by the action of 5- lipoxygenase (5-LO) and thereby converted to leukotriene (LT) A4, and further converted to LTB4, LTC4, LTD4, LTE4 and the like by the enzymatic activities of LTA4 hydrolase, LTC4 synthase, glutathione S-transferase and the like [Goodman & Gilman, Pharmacological Basis of Therapeutics, 9th edition, p. 801, 1999 (Hirokawa Shoten); Funk, C. D. , SCIENCE, vol. 294, p. 1871, 2001].
Prostaglandins bind to each specific receptor to cause inflammatory reactions such as fervescence, enhancement of vascular permeability, vasodilation, swelling and pain, bronchial smooth muscle contraction, platelet aggregation, tumor cell proliferation, enhancement of bone resorption, nerve cell degeneration and the like, and thus play important roles in expression of symptoms or pathological formation for various diseases.
Leukotrienes are physiologically active substances which bind to each specific receptor to cause inflammatory reactions such as excessive accumulation of leucocytes and enhancement of vascular permeability, smooth muscle contraction, mucus secretion, proliferation of tumor cells and the like, and thus play important roles in expression of symptoms or pathological formation for various diseases.
Although inflammatory reactions themselves are essential reactions for living bodies to survive when they face pathogenic substances and affections, they are sometimes excessively caused or continue without any reason for providing evident benefit under certain situations or in certain diseases [Goodman & Gilman, Pharmacological Basis of Therapeutics, 9th edition, p. 827, 1999 (Hirokawa Shoten)].
The condition of living body referred to in this specification wherein an acute or chronic inflammatory reaction is observed means a condition that an excessive or unbeneficial acute or temporary inflammatory reaction or chronic and persistent inflammatory reaction is caused. Further, an inflammatory reaction refers to a series of events caused by stimuli, for example, physical hazards such as heat, infective substances, ischemia, antigen/antibody reaction and the like, and it is accompanied by flare, swelling, hyperalgesia, algesic onset and the like as well- known macroscopic clinical symptoms. It is known that, as histological mechanisms for these reactions, vasodilation, enhancement of vascular permeability, infiltration of leucocytes and phagocytes, histological decomposition and fibrosing and the like are caused [Goodman & Gilman, Pharmacological Basis of Therapeutics, 9th edition, p. 827, 1999 (Hirokawa Shoten) ]. It is known that many of these histological reactions are caused by prostaglandins and/or leukotrienes, and prostaglandins and/or leukotrienes plays important roles in inflammatory reactions.
For example, it was reported that, in a pathological tissue of rheumatoid arthritis, which is an autoimmune and chronic inflammatory disease, expression of COX-2 and production of PGE2 and TXA2 as well as expression of 5-LO and production of LTB4 were observed (Bonnet et al. , Prostaglandins, 1995, vol. 50, p. 127), and in a mouse deficient in FLAP, which is a protein required for activation of 5-LO, symptom of collagen-induced arthritis, which is a pathological model of chronic rheumatoid arthritis, was milder compared with that in a wild-type mouse (Griffiths et al. , J. Exp. Med. , 1997, vol. 185, p. 1123), and thus it has been suggested that prostaglandins and leukotrienes play important roles in the pathological formation of chronic rheumatoid arthritis.
It was reported that, in a pathological tissue of bronchial asthma, one of chronic allergic diseases, excessive production of PGD2 and TXA2 as well as excessive production of LTC4 and LTD4 were observed (Wenzel et al. , Am Rev.
Respir. Dis. , 1990, vol. 142, p. 112), and an airway hypersensitive reaction, which is a pathological model of bronchial asthma, was unlikely to occur in a PGD2 receptor- deficient mouse (Matsuoka et al. , SCIENCE, vol. 287, p. 2013,2000). Thus, it has been demonstrated that roles of prostaglandins and leukotrienes are important in bronchial asthma.
In a cerebral tissue after ischemic reperfusion, expression of COX-2 increased, and concentrations of PGL2 and TXAz increased, whereas activity of 5- LO increased, and production amount of LTC4 increased (Ohtsuki et al. , Am. J.
Physiol. , 1995, vol. 268, p. 1249). Thus, it is known that prostaglandins and leukotrienes play important roles in formation of infarct that is accepted as an ischemic reperfusion injury.
It has been revealed that, in a pathological tissue of Alzheimer's disease, one of the diseases with neurodegeneration, the COX activity and 5-LO activity increased, prostaglandins and leukotrienes cause formation of the ß-amyloid protein, one of the pathogenic substances of Alzheimer's disease, and further cause degeneration of nerve cells (Sugaya et al., Jpn. J. Pharmacol. , 2000, vol. 82, p. 85), and thus it is believed that prostaglandins and leukotrienes play important roles in the formation of neurodegenerative diseases such as Alzheimer's disease.
Furthermore, for example, it was reported that, in a pathological tissue of colon cancer, COX and 5-LO were expressed, and amounts of production of prostaglandins and leukotrienes were increased (Dreyling et al. , Biochim. Biophys.
Acta. , 1986, vol. 878, p. 184), and leukotriene caused increase in colon cancer cells (Qiao et al. , Biochim. Biophys. Acta, 1995, vol. 1258, p. 215 ; Hong et al. , Cancer Res., 1999, vol. 59, p. 2223). Thus, it is believed that prostaglandins and leukotrienes play important roles also in tissues of large bowel cancer.
Involvement of prostaglandins and/or leukotrienes in diseases and pathological conditions is not limited to those diseases exemplified above, and it has been demonstrated that prostaglandins and/or leukotrienes are involved in variety of conditions, various diseases, or various pathological conditions where acute or chronic inflammatory reactions are observed and their roles are important.
For the above reason, various prostaglandin production suppressors or leukotriene production suppressors are used as agents for prophylactic or therapeutic treatment of conditions, various diseases or pathological conditions where an acute or chronic inflammatory reaction is recognized. Various non- steroidal anti-inflammatory drugs (NSAIDS) as medicaments having a prostaglandin production-suppressing action are available and used as therapeutic agents for chronic rheumatoid arthritis and osteoarthritis, antiphlogistic-analgesic agents for injury and the like, prophylactic agents for cerebral infarction or myocardial infarction, prophylactic agents for colon polyposis and the like.
However, the class of NSAIDS suppress only production of prostaglandins, and as a result, they increase amounts of production of leukotrienes, and exhibit side effects such as asthmatic attack and gastrointestinal injury as well as renal disturbance.
Furthermore, a difference between an effective dose and a dose inducing the side effects is small in these NSAIDS, and no satisfactory agent is available from a viewpoint of therapeutic effect. A 5-LO inhibitor is available which is described in European Patent No. 279263 as a medicament having a leukotriene production- suppressing action, and the inhibitor is known as a prophylactic agent for asthma.
However, since the agent causes side effects such as hepatic disorder, its dosage is limited, and the agent is not satisfactory also from a viewpoint of therapeutic effect.
Since steroid agents suppress production of both of prostaglandins and leukotrienes, they are used as prophylactic agents or therapeutic agents for conditions of living bodies, various diseases and pathological conditions where various acute or chronic inflammatory reactions are observed. However, their actions are not limited to the lipid mediator production-suppressing action, and they exhibit severe side effects such as induction and exacerbation of infectious diseases due to the immunosuppression action, growth retardation due to normal cell antiproliferative activity, anetoderma and peptic ulcer. Therefore, their uses are limited.
Furthermore, for the above reasons, it is considered that compounds, that suppress the production of both of prostaglandins and leukotrienes and have reduced side effect, are effective as therapeutic agents or prophylactic agents for such conditions of living bodies, diseases or pathological conditions in mammals as described above, and methods of using such compounds together with medicaments available at present are more effective therapeutic or prophylactic methods.
Therefore, development of compounds suppressing the production of both of prostaglandins and leukotrienes, and manufacture of pharmaceutical preparations thereof are strongly desired.
As compounds structurally similar to the compounds of the present invention, for example, biphenyl-5-alkanoic acid derivatives and use thereof are described in W099/19291. However, the moiety of these compounds that corresponds to"AR"included in the formula (I) of the compounds of the present invention is phenyl group, and thus structural features of the above compounds are different. Further, biaryl phospholipase A2 inhibitors are described in U. S. Patent No. 5,391, 817 Japanese Patent Unexamined Publication (Kokai) No. 7-22399].
However, the moiety of these compounds that corresponds to"AR"included in the formula (I) of the compounds of the present invention is only defined to be phenyl group, and thus the structural features of the above compounds are different.
Bicyclic heterocyclic compounds are described in WO00/35886 as protease inhibitors.
However, the substituents of these compounds on the moiety that corresponds to "AR"included in the formula (I) of the compounds of the present invention are different, and further, the publication is completely silent about whether or not the compounds described in the above patent document have any prostaglandin production-suppressing action or leukotriene production-suppressing action.
[Patent document 1] W099/19291 [Patent document 2] U. S. Patent No. 5,391, 817 [Patent document 3] WO00/35886 Disclosure of the Invention An object of the present invention is to provide a novel compound having superior prostaglandin production-suppressing action and leukotriene production- suppressing action. Another object of the present invention is to provide a compound for prophylactic and/or therapeutic treatment of various inflammatory diseases, autoimmune diseases, allergic diseases, pain and fibrosis in mammals caused by lipid mediators. A further object of the present invention is to provide a pharmaceutical composition containing such a compound. A still further object of the present invention is to provide an intermediate for the production of the compound. These objects and other objects as well as advantages of the present invention will be apparent for those skilled in the art from the following descriptions.
In order to achieve the aforementioned objects, the inventors of the present invention conducted various researches. As a result, they found that the substituted arylalkanoic acid derivatives represented by the following general formula, which are novel compounds, had superior prostaglandin production- suppressing action and leukotriene production-suppressing action, and thus accomplished the present invention..
The present invention is embodied by, for example, those described in the following (1) to (191).
(1) A compound represented by the formula (I): [In the formula, Link represents a saturated or unsaturated straight hydrocarbon chain having 1 to 3 carbon atoms.
C2, C3, C4, C5, and C6 in the aromatic ring (E) independently represent a ring-constituting carbon atom. One of the ring-constituting carbon atoms to which Rs and AR do not bind may be replaced with V.
V represents nitrogen atom, or carbon atom substituted with Zx. Zx represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, nitro group, -OR9, or-N (Rnl) (Rn2). R9 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or-A6- Qp, wherein A6 represents a single bond or methylene, Qp represents phenyl group, and the phenyl group may be substituted with one of T1 or two or more of the same or different T1. T1 represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, hydroxyl group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, nitro group, an alkoxy group having 1 to 4 carbon atoms, or a mono-or dialkylamino group having 1 to 4 carbon atoms. Rn'represents hydrogen atom or a linear or branched saturated alkyl group having 1 to 4 carbon atoms, Rn2 has the same meaning as Rnl, or represents-COR23 or-SO2R24, or binds to Rn1 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group. R23 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms,-O-A6-Qp, or-N (R25) (R26).
R25 represents hydrogen atom, or a linear or branched saturated alkyl group having 1 to 4 carbon atoms. R26 has the same meaning as R25, or binds to R25 to form a 3- to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group. R24 represents a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono- or dialkylamino group having 1 to 4 carbon atoms.
Rs represents-D-Rx or-N (Ry) (Rz).
D represents a single bond, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or C (0)-.
Rx represents a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or represents Ra represented by the following formula: RI (CH2) k- (Ra) Rb represented by the following formula: or Rc represented by the following formula : k in Ra represents 0 or an integer of 1 to 3. RI represents a saturated cyclic alkyl group having 3 to 7 carbon atoms, or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms, and R1 may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms. Q in Rb represents a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or a heterocyclic ring (q), and binds to A2 at an arbitrary position. The heterocyclic ring (q) contains the same or different 1 to 4 ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. A1 represents a single bond or an alkylene (a) having 1 to 3 carbon atoms, and the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group. A2 represents a single bond, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-N (R4)- (provided that when A2 represents oxygen atom, sulfur atom,-S (O)-,-S (0) 2-or-N (R4)-, A1 represents ethylene or trimethylene). R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,-OR5,-N (R6) (R6'),-NHCOR7,- NHS02R8, or-A6-Qa, or they bind to each other to represent methylenedioxy group.
Qa represents a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or a heterocyclic ring (qa), binds to As at an arbitrary position on the ring, and may be substituted with one of T1 or two or more of the same or different T1. The heterocyclic ring (qa) contains the same or different 1 to 4 ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. R5 and R7 independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or-A6-Qa. R8 represents a lower alkyl group having 1 to 4 carbon atoms.
Rs'has the same meaning as R6, or binds to R6 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogen-containing cycloalkyl group or morpholino group. p in Rc represents an integer of 2 to 4. A4 represents a single bond, methylene, or ethylene. A5 represents-C (O)-,-C (S)-, or-S (0) 2-. Rd represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa. Re represents an alkyl group having 1 to 8 carbon atoms,-A6-Qa,-(CH2) iR14,-OR23,-SR23, or-N (R29) (R30). i represents an integer of 1 to 3, R14 represents hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N-dialkylcarbamoyl group having 1 to 4 carbon atoms. R28 represents an alkyl group having 1 to 8 carbon atoms, or-A6-Qa.
R29 represents an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or-A6-Qa. R30 represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogen-containing cycloalkyl group or morpholino group.
Rz has the same meaning as Rx, or Rz represents methyl group, ethyl group, or-A5-Re. Ry represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or-A6-Qp, or Ry may bind to Rz to form, together with a nitrogen atom to which they bind, a saturated or unsaturated 3 to 7-membered nitrogen-containing cyclic group, wherein said nitrogen-containing cyclic group may optionally be substituted with one or two lower alkyl groups having 1 to 4 carbon atoms wherein said two alkyl groups may be the same or different.
AR represents a partially unsaturated or completely unsaturated condensed bicyclic carbon ring or a heterocyclic ring (ar), and may be substituted with one of Xa or two or more of the same or different Xa. The heterocyclic ring (ar) contains the same or different 1 to 4 ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. Xa represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, a saturated cyclic alkyl group having 3 to 7 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group,-(CH2) iRl4,-ORl°,-N (Rll) (Rl2), -SO2Rl3, or-COR27. Rlo represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or- (CH2) iRl4. R"represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. R12 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms, -COR15, or-S02Rl6, or binds to Rll to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogen-containing cycloalkyl group or morpholino group. Rl5 represents a lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms, amino group, a mono-or dialkylamino group having 1 to 4 carbon atoms, or-A6-Qa. R13 and Rl6 independently represent a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono-or dialkylamino group having 1 to 4 carbon atoms. R27 represents hydrogen atom, hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono-or dialkylamino group having 1 to 4 carbon atoms.
Y represents hydrogen atoin, a lower alkyl group having 1 to 4 carbon atoms,- (CH2) mN (Ri8) (Ri9), or-C (R20) 2OC (O) A3R21. Symbol m represents an integer of 2 or 3. Rl8 is the same as Rl9, or binds to Rl9 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogen-containing cycloalkyl group or morpholino group. R19 represents methyl group, ethyl group, or propyl group. R20 represents hydrogen atom, methyl group, ethyl group, or propyl group. R21 represents a lower alkyl group having 1 to 4 carbon atoms, a cyclic saturated alkyl group having 3 to 6 carbon atoms, or phenyl group, and A3 represents a single bond, or oxygen atom. This compound may sometimes be hereinafter referred to simply as"Compound (I)"of the present invention. "] or a salt thereof.
(1-2) The compound or salt thereof according to (1), wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 1 to 3, Rz has the same meaning as that of Rx or represents-A5-Re when Rs is-N (Ry) (Rz), and Ry is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or A6-Qp, or Ry binds to Rz to form, together with a nitrogen atom to which they bind, a saturated or unsaturated 3 to 7-membered nitrogen-containing cyclic group.
(2) The compound or salt thereof according to (1) or (1-2) mentioned above, wherein, in the formula (I), AR binds to any atom among C2 and C3 in the aromatic ring (E).
(3) The compound or salt thereof according to any one of (1) to (2) mentioned above, wherein, in the formula (I), n is an integer of 2 (the description of"according to any one of (1) to (2) "includes (1-2) mentioned above, and the same or similar description should be construed in the same manner hereinafter in the specification).
(4) The compound or salt thereof according to any one of (1) to (3) mentioned above, wherein, in the formula (I), AR is a residue of naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-lH-quinoline, benzo [d] isothiazole, 1H-indazole, benzo [c]isothiazole, 2H- indazole, imidazo [1, 2-a]pyridine, 1H-pyrrolo [2, 3-b] pyridine, isoquinoline, dihydro- 2H-isoquinoline, cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole, 1H-pyrrolo [3, 2-b] pyridine, benzo [1, 2,5] thiadiazole, 1H-benzotriazole, 1, 3-dihydropyrrolo [2, 3-b] pyridine, 1, 3-dihydrobenzimidazole, dihydro-3H- benzoxazole, phthalazine, [1, 8] naphthalidine, [1, 5] naphthalidine, lH-pyrrolo [3, 2- c] pyridine, lH-pyrrolo [2, 3-c]pyridine, 1H-pyrazolo [4, 3-b] pyridine, lH-pyrazolo [4,3- c] pyridine, lH-pyrazolo [3, 4-c]pyridine, 1H-pyrazolo [3, 4-b] pyridine, [1, 2, 4] triazolot4, 3-a] pyridine, thieno [3, 2-c] pyridine, thieno [3, 2-b]pyridine, 1H- thieno [3, 2-c] pyrazole, benzo [d] isoxazole, benzo [c] isoxazole, indolizine, 1, 3- dihydroindole, 1H-pyrazolo [3, 4-d] thiazole, 2H-isoindole, [1, 2,4] triazolo [1, 5- a] pyrimidine, lH-pyrazolo [3, 4-b]pyrazine, 1H-imidazo [4, 5-b]pyrazine, 7H-purine, or 4H-chromene (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa).
(5) The compound or salt thereof according to any one of (1) to (3) mentioned above, wherein, in the formula (I), AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [blthiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro- 3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H- benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin- 6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c]isothiazol-5-yl group, benzo [c]isothiazol-4-yl group, benzo [clisothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b]pyridin-5-yl group, lH-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7- yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7- yl group, lH-pyrrolo [3, 2-b] pyridin-5-yl group, lH-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2, 5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- c] pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin- 5-yl group, 1H-pyrrolo[2,3-c]pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b]pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, lH-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2, 4] triazolo [4, 3-a]pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3,2- e] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3, 2- b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa).
(6) The compound or salt thereof according to any one of (1) to (3) mentioned above, wherein, in the formula (I), AR is a residue of naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-lH-quinoline, benzo [d]isothiazole, 1H-indazole, benzo[c]isothiazole, 2H- indazole, imidazo [1, 2-a]pyridine, 1H-pyrrolo [2, 3-b] pyridine, isoquinoline, or dihydro-2H-isoquinoline (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa).
(7) The compound or salt thereof according to any one of (1) to (3) mentioned above, wherein, in the formula (I), AR is a residue of cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole, lH-pyrrolo [3, 2-b] pyridine, benzo [1, 2,5] thiadiazole, 1H-benzotriazole, 1, 3-dihydropyrrolo [2, 3-b] pyridine, 1,3-dihydrobenzimidazole, dihydro-3H-benzoxazole, phthalazine, [1, 8] naphthalidine, [1, 5] naphthalidine, 1H- pyrrolo [3, 2-c]pyridine, 1H-pyrrolo [2, 3-c]pyridine, 1H-pyrazolo [4, 3-b] pyridine, 1H- pyrazolo [4, 3-c]pyridine, 1H-pyrazolo [3, 4-c]pyridine, 1H-pyrazolo [3, 4-b] pyridine, [1, 2,4] triazolo [4, 3-a] pyridine, thieno [3, 2-c] pyridine, thieno [3, 2-b] pyridine, 1H- thieno [3, 2-c] pyrazole, benzo [d] isoxazole, benzo [c] isoxazole, indolizine, 1, 3- dihydroindole, lH-pyrazolo [3, 4-d] thiazole, lH-pyrazolo [3, 4-d] thiazole, 2H-isoindole, [1, 2,4] triazolo [1, 5-a] pyrimidine, lH-pyrazolo [3, 4-b] pyrazine, lH-imidazo [4, 5- b] pyrazine, 7H-purine, or 4H-chromene (the aforementioned residue may have one of Xa or two or more of the same or different Xa).
(8) The compound or salt thereof according to any one of (1) to (7) mentioned above, wherein, in the formula (I), Rs is-D-Rx or-N (Ry) (Rz), D is a single bond, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-C (O)-, Rx is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, Rl is a saturated cyclic alkyl group having 3 to 7 carbon atoms or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms, Rl may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, 4H-chromenyl group, dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group, 1, 3-dihydrobenzimidazole group, dihydro-3H-benzoxazole group, or dihydro-3H-benzothiazole group (the aforementioned groups binds to A2 at an arbitrary position), Al is a single bond or an alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group, A2 is a single bond, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-N (R4)- (provided that when A2 represents oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-N (R4)-, A1 represents ethylene or trimethylene), R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,- OR5,-N (R6) (R6'),-NHCOR7,-NHSO2R3, or-A6-Qa, or they bind to each other to represent methylenedioxy group, Qa is phenyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, or indazolyl group (these groups may be substituted with one of Tl or two or more of the same or different T1, and bind to As at an arbitrary position on the ring), R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R5 and R7 independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or-A6-Qa, R3 is a lower alkyl group having 1 to 4 carbon atoms, R6 has the same meaning as R6, or binds to R6 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group, p in Rc is an integer of 2 to 4, A4 is a single bond or methylene or ethylene, A5 is-C (0)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa, Re is an alkyl group having 1 to 8 carbon atoms,-A6-Qa, - (CH2) iRl4,-OR28,-SR28, or-N (R29) (R30), i is an integer of 1 to 3, R14 is hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N- dialkylcarbamoyl group having 1 to 4 carbon atoms, R28 is an alkyl group having 1 to 8 carbon atoms or-As-Qa, R29 is an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or-A6-Qa group, R30 is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3- to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group, Rz has the same meaning as Rx, or is-A5-Re, and Ry is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or-A6-Qp, or binds to Rz to form a saturated or unsaturated nitrogen-containing cyclic substituent having 3 to 7 atoms together with nitrogen atom to which they binds.
(9) The compound or salt thereof according to any one of (1) to (8) mentioned above, wherein, in the formula (1), among C2, C3, C4, C5, and C6 in the aromatic ring (E), one ring-constituting atom to which Rs or AR does not bind is replaced with nitrogen atom.
(10) The compound or salt thereof according to any one of (1) to (8) mentioned above, wherein, in the formula (1), among C2, C3, C4, C5, or C6 in the aromatic ring (E), one ring-constituting atom to which Rs or AR does not bind is replaced with- N (Rnl) (Rn2) (provided that one of Rnl and Rn2 represents a substituent other than hydrogen atom).
(11) The compound or salt thereof according to (1) or (10) mentioned above, wherein, in the formula (1), Rs is-O-Rx.
(12) The compound or salt thereof according to any one of (1) to (11) mentioned above, wherein, in the formula (1), Rs is-O-Rc.
(13) The compound or salt thereof according to any one of (1) to (10) mentioned above, wherein, in the formula (I), Rs is-N (Ry) (Rz).
(14) The compound or salt thereof according to any one of (1) to (10) mentioned above, wherein, in the formula (1), Rs is-D-Rx, and D is a single bond, sulfur atom, -S (O)-,-S (0) 2-, or-C (O)-.
(15) The compound or salt thereof according to any one of (1) to (10) mentioned above, wherein, in the formula (I), Rs is-S-Rx.
(16) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (1), AR binds at the position of C2 in the aromatic ring (E), and Rs binds to one of the ring-constituting carbon atoms C3, C4, and C5.
(17) The compound or salt thereof according to (16) mentioned above, wherein, in the formula (I), Rs is-O-Rx, and no ring-constituting carbon atom in the aromatic ring (E) is replaced with V.
(18) The compound or salt thereof according to (16) or (17) mentioned above, wherein, in the formula (I), n is an integer of 2, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(19) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (1), Link is- (CH2) n-, n is an integer of 2, AR binds at the position of C2 in the aromatic ring (E), Rs binds to one of ring-constituting carbon atoms C3, C4 and C5, Rs is-O-Rx, Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V.
(20) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (I), Link is- n-, n is an integer of 2, AR binds at the position of C2 in the aromatic ring (E), Rs binds to one of ring-constituting carbon atoms C3, C4 and C5, Rs is-O-Rx, Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V.
(21) The compound or salt thereof according to any one of (16) to (20) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(22) The compound or salt thereof according to any one of (16) to (21) mentioned above, wherein, in the formula (I), Rs is-O-Rx, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, a methylene group substituted with methyl group or ethyl group, or unsubstituted methylene group, or an ethylene group substituted with methyl group or ethyl group, or unsubstituted ethylene group, A2 is a single bond, oxygen atom, sulfur atom, -N (methyl) -, or- N (ethyl) - (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene), and R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(23) The compound or salt thereof according to any one of (16) to (22) mentioned above, wherein, in the formula (1), Rx-D-binds at the position of C3 in the aromatic ring (E).
(24) The compound or salt thereof according to any one of (16) to (22) mentioned above, wherein, in the formula (I), Rx-D-binds at the position of C4 in the aromatic ring (E).
(25) The compound or salt thereof according to any one of (16) to (22) mentioned above, wherein, in the formula (1), Rx-D-binds at the position of C5 in the aromatic ring (E).
(26) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 1 to 3, AR binds to C2, Rs binds to one of the ring- constituting carbon atoms C3, C4, and C5, a ring-constituting atom among C3, C4, and C5 to which Rs does not bind may be replaced with V, V is nitrogen atom or carbon atom substituted with Zx, Zx is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is-D-Rx or-N (Ry) (Rz), D is oxygen atom or sulfur atom, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2- cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, and A2 is a single bond, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl) - (provided that when A2 is oxygen atom, sulfur atom, -N (methyl) -, or-N (ethyl)-, Al represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
Symbol p in Rc is an integer of 2 or 3, A4 is a single bond or methylene, A5 is-C (O)-, -C (S)-, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4- fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4- methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen- 2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4'methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3- fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5- methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan- 2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6- dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, l- (3'chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2- methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2- fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4- chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4- difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2-13- (trifluoromethyl) phenyl] ethyl group, 2-14- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry is hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group, or pyrazol-1-yl group together with nitrogen atom to which they binds, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, lH-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [clisothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, lH-pyrrolo [2,3- blpyridin-5-yl group, lH-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [l, 2, 5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b]pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, lH-pyrrolo [3, 2- c]pyridin-6-yl group, lH-pyrrolo [3, 2-c]pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin- 5-yl group, lH-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, l H-pyrazolo [3, 4-b]pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2- b]pyridin-6-yl group, 1H-thieno [3, 2-c]pyrazol-5-yl group, lH-thieno [3, 2-c]pyrazol-4- yl group, benzo [d]isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d]isoxazol-7-yl group, benzo[c]isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group or ethyl group.
(27) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C2 is carbon atom to which AR binds, C3 is carbon atom to which Rs binds, C4 may be replaced with V, C5 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N- dimethylamino group, Rs is-O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2-(4-fluorophenyl) ethyl group, 2-(2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzolb] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d]isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(28) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C2 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 may be replaced with V, C3 and C6 represents an unsubstituted ring-constituting carbon atom, V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N- dimethylamino group, Rs is-O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyllethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyll ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(29) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), and Rs binds to C5 or C6 in the aromatic ring (E).
(30) The compound or salt thereof according to (29) mentioned above, wherein, in the formula (I), Rs is-O-Rx, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V.
(31) The compound or salt thereof according to (29) or (30) mentioned above, wherein, in the formula (I), n is an integer of 2, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(32) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (1), Link is-(CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to the ring-constituting carbon atom C5 or C6 in the aromatic ring (E), Rs is-O-Rx, Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V.
(33) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (I), n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to the ring-constituting carbon atom C5 or C6 in the aromatic ring (E), Rs is-O-Rx, Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, and all of C2, C3, C4, C5, and C6 in the aromatic ring (E) are not replaced with V.
(34) The compound or salt thereof according to any one of (29) to (33) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(35) The compound or salt thereof according to any one of (29) to (34) mentioned above, wherein, in the formula (I), Rs is-O-Rx, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, or methylene group substituted with methyl group or ethyl group or unsubstituted methylene group, or ethylene group substituted with methyl group or ethyl group or unsubstituted ethylene group, A2 is a single bond, oxygen atom, sulfur atom,-N (methyl)-, or- N (ethyl) - (provided that when A2 is oxygen atom, sulfur atom, -N (methyl) -, or- N (ethyl)-, Al is ethylene), and R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(36) The compound or salt thereof according to any one of (29) to (35) mentioned above, wherein, in the formula (I), Rs binds at the position of C5 in the aromatic ring (E).
(37) The compound or salt thereof according to any one of (29) to (35) mentioned above, wherein, in the formula (I), Rs binds at the position of C6 in the aromatic ring (E).
(38) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C3 is carbon atom to which AR binds, C5 is carbon atom to which Rs binds, C2, C4 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2' (4'methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenylbxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, l-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-methyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a]pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolol2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(39) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), and C6 is replaced with V.
(40) The compound or salt thereof according to (39) mentioned above, wherein, in the formula (I), n is an integer of 2, V is carbon atom substituted with Zx, Rs is-O- Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(41) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), Cs is carbon atom substituted with Zx, Rs is-O-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(42) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C6 is carbon atom substituted with Zx, Rs is-0-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(43) The compound or salt thereof according to any one of (39) to (42) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(44) The compound or salt thereof according to any one of (39) to (43) mentioned above, wherein, in the formula (I), Rs is-O-Rx, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, or methylene group substituted with methyl group or ethyl group or unsubstituted methylene group, or ethylene group substituted with methyl group or ethyl group or unsubstituted ethylene group, A2 is a single bond, oxygen atom, sulfur atom, -N (methyl) -, or- N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom,-N (methyl)-, or- N (ethyl)-, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(45) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C6 is carbon atom substituted with Zx, C2 and C5 are unsubstituted ring- constituting carbon atoms, Zx is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, Rs is-O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2-(4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyll ethyl group, 2- [4- (trifluoromethyl) phenyl]ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) nap hthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, l-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol- 5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indl-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [l, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(46) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, and C2 and C6 are unsubstituted ring- constituting carbon atoms.
(47) The compound or salt thereof according to (46) mentioned above, wherein, in the formula (I), n is an integer of 2, D is oxygen atom, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(48) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is'O'Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(49) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (1), Link is- (CH2)"-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(50) The compound or salt thereof according to any one of (46) to (49) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(51) The compound or salt thereof according to any one of (46) to (50) mentioned above, wherein, in the formula (I), Rs is-O-Rx, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, or methylene group substituted with methyl group or ethyl group or unsubstituted methylene group, or ethylene group substituted with methyl group or ethyl group or unsubstituted ethylene group, A2 is a single bond, oxygen atom, sulfur atom,-N (methyl)- or- N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom,-N (methyl)-, or- N (ethyl)-, Al is ethylene), and R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(52) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 is nitrogen atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4'fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2-(2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyll ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino)ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino)naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-1H-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(53) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring- constituting carbon atoms, Rs is-D-Rx, and D is a single bond, sulfur atom,-S (O)-,- S (0) 2-, or-C (O)-.
(53-2) The compound of salt thereof according to (1-2) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, C2 and C6 are unsubstituted ring- constituting carbon atoms, Rs is-D-Rx, and D is a single bond, sulfur atom,-S (O)-,- S (0) 2-, or-C (O)-.
(53-3) The compound or salt thereof according to (53) or (53-2) mentioned above, wherein, in the formula (I), Rs is-D-Rx and D is single bond.
(54) The compound or salt thereof according to any one of (53) to (53-3) mentioned above, wherein, in the formula (I), n is an integer of 2, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(55) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-D-Rx, D is a single bond, sulfur atom,-S (O)-,-S (0) 2-, or-C (O)-, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(55-2) The compound or a salt thereof according to (4) mentioned above, wherein, in the formula (1), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-D-Rx, D is a single bond, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(56) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-D-Rx, D is a single bond, sulfur atom,-S (O)-,-S (0) 2-, or-C (O)-, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(56-2) The compound or a salt thereof according to (5) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-D-Rx, D is a single bond, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(57) The compound or salt thereof according to any one of (53) to (56-2) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(58) The compound or salt thereof according to any one of (53) to (57) mentioned above, wherein, in the formula (I), Rs is-D-Rx, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, or methylene group substituted with methyl group or ethyl group or unsubstituted methylene group, or ethylene group substituted with methyl group or ethyl group or unsubstituted ethylene group, A2 is a single bond, oxygen atom, sulfur atom, -N (methyl) -, or- N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)- or-N (ethyl)-, A1 represents ethylene), and R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, A is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(58-2) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 1 to 3, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom or V is carbon atom substituted with Zx, Zx is any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group, Rs is-D-Rx, D is a single bond, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2- cyclohexylethyl group, or Rx is Rb or Rc (provided that Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group), A2 is a single bond, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)- or- N (ethyl)-, Al represents ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group, (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom). p in Rc is an integer of 2 or 3, A4 is a single bond or methylene, A5 is-C (O)-,-C (S)-, or'S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzold] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, lH-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2,3- b] pyridin-5-yl group, lH-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [l, 2,5] thiadiazol-5-yl group, benzol, 2, 5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- cjpyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin- 5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c]pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b]pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-7-yl group, thieno [3, 2-c]pyridin-2-yl group, thieno [3,2- c]pyridin-3-yl group, thieno [3, 2-c]pyridin-6-yl group, thieno [3, 2-b\pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, lH-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, lH-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
(58-3) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (1), n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom or V is carbon atom substituted with Zx, Zx is any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group, Rs is-D-Rx, D is a single bond, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2, 3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4- methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2, 3- difluorophenyl group, 2,4-difluorophenyl group, 2, 5-difluorophenyl group, 3, 4- difluorophenyl group, 2, 3-dichlorophenyl group, 2,4-dichlorophenyl group, 2,5- dichlorophenyl group, 2,6-dichlorophenyl group, 3, 4-dichlorophenyl group, 3, 5- dichlorophenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4- (N, N-dimethylamino) phenyl group, indan- 2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan- 2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2- yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan- 2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6- dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, biphenyl-2-yl group, biphenyl 3-yl group, biphenyl-4- yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3- fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, l' (3'chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2- methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2- fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4- chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4- difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2- methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b]thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo[b]thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, l-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1-(2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo[1,2-a]pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(58-4) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (1), n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom or V is carbon atom substituted with Zx, Zx is any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group, Rs is-D-Rx, D is a single. bond, Rx is phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 3,5- dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4- methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2,3- difluorophenyl group, 2, 4-difluorophenyl group, 2,5-difluorophenyl group, 3,4- difluorophenyl group, 2, 3-dichlorophenyl group, 2,4-dichlorophenyl group, 2,5- dichlorophenyl group, 2,6-dichlorophenyl group, 3,4-dichlorophenyl group, 3, 5- dichlorophenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4- (N, N-dimethylamino) phenyl group, indan- 2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan- 2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2- yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan- 2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6- dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1H-indazol-5-yl group, or 1-methyl-lH-indazol-5-yl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, l-ethyl-3- methyl-lH-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, l-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(58-5) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (1), n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C2, C5, and C6 are unsubstituted ring-constituting carbon atoms, Rs is-D-Rx, D is a single bond, Rx is phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3- dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3- methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenyl group, 3- fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2,3-difluorophenyl group, 2, 4-difluorophenyl group, 2, 5-difluorophenyl group, 3, 4-difluorophenyl group, 2, 3-dichlorophenyl group, 2,4- dichlorophenyl group, 2,5-dichlorophenyl group, 2,6-dichlorophenyl group, 3,4- dichlorophenyl group, 3,5-dichlorophenyl group, 2-trifluoromethylphenyl group, 3- trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4- (N, N- dimethylamino) phenyl group, indan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, lH-indazol-5-yl group, or 1-methyl-lH- indazol-5-yl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, l-ethyl-3- methyl-lH-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-l-propyl-lH- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(59) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 1 to 3, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is-S-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bond, oxygen atom, sulfur atom,- N (methyl) -, or-N (ethyl) - (provided that when A2 is oxygen atom, sulfur atom,- N (methyl) -, or-N (ethyl)-, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom), p in Rc is an integer of 2 or 3, A4 is a single bond or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- 1H-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [clisothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3- b]pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b]pyridin-4-y] group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol]-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, lH-pyrrolo [3,2- c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin- 5-yl group, lH-pyrrolo [2, 3-c] pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, lH-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-e] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, 1H-thieno [3, 2-c]pyrazol-5-yl group, lH-thieno [3, 2-c]pyrazol-4- yl group, benzo[d]isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b]pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
(59-2) The compound or salt thereof according to (1) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring- constituting carbon atoms, and Rs is-N (Ry) (Rz).
(59-3) The compound or salt thereof according to (1) mentioned above, wherein, in the formula (I), AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, C2 and C6 are unsubstituted ring- constituting carbon atoms, and Rs is-N (Ry) (Rz).
(60) The compound or salt thereof according to (59-2) or (59-3) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(61) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (1), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(61-2) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(62) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (1), Link is- H2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(62-2) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (1), Link is- H2) n, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is nitrogen atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(63) The compound or salt thereof according to any one of (59-2) to (62-2) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(64) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (1), n is an integer of 1 to 3, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C2, C5, and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1-(2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyll ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group, or pyrazol-1-yl group together with the nitrogen atom to which they bind, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [blthiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, 1H-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [clisothiazol-4-yl group, benzo [clisothiazol-6-yl group, benzo [clisothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, lH-pyrrolo [2,3- blpyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, l H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b]pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, lH-pyrrolo [3,2- c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin- 5-yl group, 1H-pyrrolo [2, 3-c]pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c]pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, 1H-thieno [3, 2-c]pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c]isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, lH-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, lH-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (these groups may be substituted with one of Xa or two or more of the same or different Xa), Xa represents oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2- hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
(65) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C2, C5 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, l' (3'chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2-t3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-l-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, or morpholino group together with the nitrogen atom to which they bind, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, l-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3- methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [l, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(65-2) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), Link is-(CH2) n-, n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C2, C5 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), and the group represented by-N (Ry) (Rz) is N, N- dimethylamino group, N-ethyl-N-methylamino group, N, N-diethylamino group, N- methyl-N-propylamino group, N-ethyl-N-propylamino group, N-isopropyl-N- methylamino group, N-ethyl-N-isopropylamino group, N-butylamino group, N- butyl-N-methylamino group, N-butyl-N-ethylamino group, N-isobutylamino group, N-isobutyl-N-methylamino group, N-ethyl-N-isobutylamino group, N- (2- ethylbutyl) amino group, N- (2-ethylbutyl)-N-methylamino group, N- cyclopentylamino group, N-cyclopentyl-N-methylamino group, N-cyclohexylamino group, N-cyclohexyl-N-methylamino group, N-cycloheptylamino group, N- (cyclopentylmethyl) amino group, N- (cyclopentylmethyl)-N-methylamino group, N- (cyclohexylmethyl) amino group, N- (cyclohexylmethyl)-N-methylamino group, N- (2- methylphenyl) amino group, N- (4-methylphenyl) amino group, N- (2- fluorophenyl) amino group, N- (3-fluorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (2-chlorophenyl) amino group, N- (3-chlorophenyl) amino group, N- (4- chlorophenyl) amino group, N- (indan-2-yl) amino group, N- (l-phenylethyl) amino group, N- [1- (2-fluorophenyl) ethyl] amino group, N- [1- (3-fluorophenyl) ethyl] amino group, N- [1- (4-fluorophenyl) ethyl] amino group, N- [1- (2-chlorophenyl) ethyl] amino group, N- [1- (3-chlorophenyl) ethyl] amino group, N- [1- (4-chlorophenyl) ethyl] amino group, N- (2-methylphenylmethyl) amino group, N-methyl-N- (2- methylphenylmethyl) amino group, N- (3-methylphenylmethyl) amino group, N- methyl-N- (3-methylphenylmethyl) amino group, N- (4-methylphenylmethyl) amino group, N-methyl-N- (4-methylphenylmethyl) amino group, N- (2- fluorophenylmethyl) amino group, N- (2-fluorophenylmethyl)-N-methylamino group, N- (3-fluorophenylmethyl) amino group, N- (3-fluorophenylmethyl)-N-methylamino group, N- (4-fluorophenylmethyl) amino group, N- (4-fluorophenylmethyl)-N- methylamino group, N- (2-chlorophenylmethyl) amino group, N- (2- chlorophenylmethyl)-N-methylamino group, N- (3-chlorophenylmethyl) amino group, N- (3-chlorophenylmethyl)-N-methylamino group, N- (4-chlorophenylmethyl) amino group, N- (4-chlorophenylmethyl)-N-methylamino group, N- (2, 3- difluorophenylmethyl) amino group, N- (2, 3-difluorophenylmethyl)-N-methylamino group, N-(2, 4-difluorophenylmethyl) amino group, N- (2, 4-difluorophenylmethyl) -N- methylamino group, N- (2, 5-difluorophenylmethyl) amino group, N- (2, 5- difluorophenylmethyl)-N-methylamino group, N- (3, 4-difluorophenylmethyl) amino group, N- (3,4-difluorophenylmethyl)-N-methylamino group, N- (3,5- difluorophenylmethyl) amino group, N- (3, 5-difluorophenylmethyl)-N-methylamino group, N- (2, 3-dichlorophenylmethyl) amino group, N- (2, 3-dichlorophenylmethyl) -N- methylamino group, N-(2, 4-dichlorophenylmethyl) amino group, N- (2, 4- dichlorophenylmethyl)-N-methylamino group, N- (2,5-dichlorophenylmethyl) amino group, N- (2, 5-dichlorophenylmethyl)-N-methylamino group, N- (2,6- dichlorophenylmethyl) amino group, N- (2, 6-dichlorophenylmethyl) -N-methylamino group, N- (3, 4-dichlorophenylmethyl) amino group, N- (3,4-dichlorophenylmethyl)-N- methylamino group, N- (3, 5-dichlorophenylmethyl) amino group, N- (3, 5- dichlorophenylmethyl) -N-methylamino group, N-[2- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [2- (trifluoromethyl) phenylmethyll amino group, N- [3- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [3- (trifluoromethyl) p henylmethyfl amino group, N- [4- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [4- (trifluoromethyl) phenylmethyl] amino group, 1-pyrrolidino group, 1- (4- methylpiperidino) group, 1-homopiperidino group, or 4-morpholino group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b]thiophen-5-yl group, 3- methylbenzo [b]thiophen-5-yl group, 2, 3-dimethylbenzo [b]thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol]-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolot2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(65-3) The compound or salt thereof according to (1) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 is nitrogen atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-N (Ry) (Rz), and the group represented by-N (Ry) (Rz) is N, N- dimethylamino group, N-ethyl-N-methylamino group, N, N-diethylamino group, N- methyl-N-propylamino group, N-ethyl-N-propylamino group, N-isopropyl-N- methylamino group, N-ethyl-N-isopropylamino group, N-butylamino group, N- butyl-N-methylamino group, N-butyl-N-ethylamino group, N-isobutylamino group, N-isobutyl-N-methylamino group, N-ethyl-N-isobutylamino group, N- (2- ethylbutyl) amino group, N- (2-ethylbutyl)-N-methylamino group, N- cyclopentylamino group, N-cyclopentyl-N-methylamino group, N-cyclohexylamino group, N-cyclohexyl-N-methylamino group, N-cycloheptylamino group, N- (cyclopentylmethyl) amino group, N- (cyclopentylmethyl)-N-methylamino group, N- (cyclohexylmethyl) amino group, N- (cyclohexylmethyl)-N-methylamino group, N- (2- methylphenyl) amino group, N- (4-methylphenyl) amino group, N- (2- fluorophenyl) amino group, N' (3'fluorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (2-chlorophenyl) amino group, N- (3-chlorophenyl) amino group, N- (4- chlorophenyl) amino group, N- (indan-2-yl) amino group, N- (1-phenylethyl) amino group, N- [1- (2-fluorophenyl) ethyl] amino group, N- [1- (3-fluorophenyl) ethyl] amino group, N- [1- (4-fluorophenyl) ethyl] amino group, N- [l- (2-chlorophenyl) ethyl] amino group, N-[1-(3-chlorophenyl) ethyl] amino group, N- [1- (4-chlorophenyl) ethyl] amino group, N- (2-methylphenylmethyl) amino group, N-methyl-N- (2- methylphenylmethyl)amino group, N-(3-methylphenylmethyl)amino group, N- methyl-N- (3-methylphenylmethyl) amino group, N- (4-methylphenylmethyl) amino group, N-methyl-N- (4-methylphenylmethyl) amino group, N- (2- fluorophenylmethyl) amino group, N- (2-fluorophenylmethyl)-N-methylamino group, N- (3-fluorophenylmethyl) amino group, N- (3-fluorophenylmethyl)-N-methylamino group, N- (4-fluorophenylmethyl) amino group, N- (4-fluorophenylmethyl)-N- methylamino group, N- (2-chlorophenylmethyl) amino group, N- (2- chlorophenylmethyl)-N-methylamino group, N- (3-chlorophenylmethyl) amino group, N- (3-chlorophenylmethyl) -N-methylamino group, N- (4-chlorophenylmethyl) amino group, N- (4-chlorophenylmethyl)-N-methylamino group, N- (2, 3- difluorophenylmethyl) amino group, N- (2, 3-difluorophenylmethyl)-N-methylamino group, N- (2, 4-difluorophenylmethyl) amino group, N- (2, 4-difluorophenylmethyl)-N- methylamino group, N- (2, 5-difluorophenylmethyl) amino group, N- (2, 5- difluorophenylmethyl)-N-methylamino group, N- (3, 4-difluorophenylmethyl) amino group, N- (3, 4-difluorophenylmethyl)-N-methylamino group, N- (3, 5- difluorophenylmethyl) amino group, N- (3, 5-difluorophenylmethyl)-N-methylamino group, N- (2,3-dichlorophenylmethyl) amino group, N- (2,3-dichlorophenylmethyl)-N- methylamino group, N- (2, 4-dichlorophenylmethyl) amino group, N- (2, 4- dichlorophenylmethyl)-N-methylamino group, N- (2, 5-dichlorophenylmethyl) amino group, N- (2, 5-dichlorophenylmethyl)-N-methylamino group, N- (2, 6- dichlorophenylmethyl) amino group, N- (2, 6-dichlorophenylmethyl)-N-methylamino group, N-(3,4-dichlorophenylmethyl)amino group, N- (3, 4-dichlorophenylmethyl) -N- methylamino group, N- (3, 5-dichlorophenylmethyl) amino group, N- (3, 5- dichlorophenylmethyl)-N-methylamino group, N- [2- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [2- (trifluoromethyl) phenylmethyl] amino group, N- [3- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [3- (trifluoromethyl) phenylmethyl] amino group, N- [4- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [4- (trifluoromethyl) phenylmethyl] amino group, 1-pyrrolidino group, 1- (4- methylpiperidino) group, 1-homopiperidino group, or 4-morpholino group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-1H- indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethy)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(66) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (1), n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is carbon atom substituted with- N (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(67) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is carbon atom substituted with -N (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is- O-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(68) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is carbon atom substituted with -N (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is- O-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(69) The compound or salt thereof according to any one of (66) to (68) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(70) The compound or salt thereof according to any one of (66) to (69) mentioned above, wherein, in the formula (I), Rs is'O'Rx, Rx is a group selected from butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, and cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, or methylene group substituted with methyl group or ethyl group or unsubstituted methylene group, or ethylene group substituted with methyl group or ethyl group or unsubstituted ethylene group, A2 represents a single bond, oxygen atom, sulfur atom,-N (methyl) -, or-N (ethyl) - (provided that when A2 is oxygen atom, sulfur atom, - N (methyl) -, or-N (ethyl)-, Al is ethylene), and R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, A is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(71) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 is carbon atom substituted with Zx, C2 and C6 are unsubstituted ring- constituting carbon atoms, Zx is N-methylamino group, N-ethylamino group, N-propylamino group, N- isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is'O'Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1-(4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6-(N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6-(2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-1H-indol- 5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-1H- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [1, 2-a]pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolol2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolol2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b]pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(72) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-D-Rc, D is oxygen atom or sulfur atom, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(73) The compound or salt thereof according to (4) mentioned above, wherein, in the formula (I), Link is- H2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rc, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(74) The compound or salt thereof according to (5) mentioned above, wherein, in the formula (I), Link is- H2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rc, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(75) The compound or salt thereof according to any one of (72) to (74) mentioned above, wherein, in the formula (I), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(76) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 1 to 3, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is-D-Rc, D is oxygen atom or sulfur atom, p in Rc is an integer of 2 or 3, A4 is a single bond or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4- chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin- 3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t- butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- 4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c]isothiazol-4-yl group, benzo [c]isothiazol-6-yl group, benzo [c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2,3- b]pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3- b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin- 5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-e] pyridin-2-yl group, thieno [3,2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c]isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2, 4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, lH-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
(77) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 2, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorine atom, chlorine atom, bromine atom, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N- isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is-O-Rc, p in Rc is an integer of 2, A4 is a single bond or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, or 4-fluorophenylmethyl group, Re is isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t- butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N- propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, pyrrolidino group, piperidino group, or morpholino group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-1H- indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
(78) The compound or salt thereof according to (7) mentioned above, wherein, in the formula (I), Link is- (CH2) n-, n is an integer of 2, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rx, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
(79) The compound or salt thereof according to (78) mentioned above, wherein, in the formula (1), Xa which may substitute on AR is methyl group, ethyl group, propyl group, hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, methylamino group, dimethylamino group, carboxyl group, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoyl group, or N, N-dimethylsulfamoyl group.
(80) The compound or salt thereof according to (78) or (79) mentioned above, wherein, in the formula (I), Rs is-O-Rx, Rx is butyl group, isobutyl group, 2- ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group, or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), Al is a single bond, or methylene group substituted with methyl group or ethyl group or unsubstituted methylene group, or ethylene group substituted with methyl group or ethyl group or unsubstituted ethylene group, A2 is a single bond, oxygen atom, sulfur atom,-N (methyl)-, or- N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom,-N (methyl)-, or- N (ethyl)-, Al is ethylene), and R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, or dimethylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom).
(81) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 1 to 3, C3 is carbon atom to which AR binds, C4 is carbon atom to which Rs binds, C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is-O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bond, oxygen atom, sulfur atom,- N (methyl) -, or-N (ethyl) - (provided that when A2 is oxygen atom, sulfur atom,- N (methyl)-, or-N (ethyl)-, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bond or unsubstituted methylene, and A2 is a single bond, one of R2 and R3 is a substituent other than hydrogen atom), p in Rc is an integer of 2 or 3, A4 is a single bond or methylene, A5 is-C (O)-,-C (S) -, or'8 (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen- 2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, AR is cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3,2- b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1,3- dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro- 3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H- benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- c] pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin- 5-yl group, lH-pyrrolo [2, 3-c]pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2- c] pyridin-3-yl group, thieno [3, 2-c]pyridin-6-yl group, thieno [3, 2-b]pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c]pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d]isoxazol- 6-yl group, benzo [d]isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, lH-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazololl, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
(82) The compound or salt thereof according to (6) mentioned above, wherein, in the formula (I), Link is- H2) n-, AR binds to C3 in the aromatic ring (E), Rs binds to C4 in the aromatic ring (E), C5 is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Rs is-O-Rx, and Rx is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra or Rb.
(83) The compound or salt thereof according to (82) mentioned above, wherein, in the formula (I), Zx is fluorine atom, chlorine atom, nitro group, amino group, methyl group, or OR9.
(84) The compound or salt thereof according to (1-2) mentioned above, wherein, in the formula (I), n is an integer of 1 to 3, AR binds to C3, Rs binds to one of the ring- constituting atoms C4, C5, and C6, a ring-constituting carbon atom to which Rs does not bind among C4, C5, and C6 may be replaced with V, V is nitrogen atom or carbon atom substituted with Zx, Zx is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, Rs is-D-Rx or-N (Ry) (Rz), D is oxygen atom or sulfur atom, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2- cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Re, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bind, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, A1 is a single bind or unsubstituted methylene, and A2 is a single bind, one of R2 and R3 is a substituent other than hydrogen atom), p in Ru vis an integer of 2 or 3, A4 is a single bind or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4- chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin- 3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N-(pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group or ethyloxyearbonylamino group, Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4- methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2- yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2- yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2- yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan- 2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7- dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4- chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2-(4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyllethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-l-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group, or pyrazol-1-yl group together with the nitrogen atom, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- 1H-quinolin-5-yl group, benzold] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, 1H-indazol-4-yl group, lH-indazol-6-yl group, benzo [c]isothiazol-5-yl group, benzo [c]isothiazol-4-yl group, benzo [c]isothiazol-6-yl group, benzo [c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, lH-pyrrolo [2,3- b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, l H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b]pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- c] pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin- 5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b]pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b]pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3,2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3, 2- b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d]isoxazol-7-yl group, benzo [c]isoxazol-5-yl group, benzo [c]isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
(85) A medicament containing a compound represented by the aforementioned formula (I) or a pharmacologically acceptable salt thereof as an active ingredient.
(86) An agent for suppressing production of a prostaglandin and/or leukotriene, which contains a compound represented by the aforementioned formula (I) or a pharmacologically acceptable salt thereof as an active ingredient.
(87) The medicament according to (85) for prophylactic and/or therapeutic treatment of a disease caused by production of a prostaglandin and/or leukotriene.
(88) The medicament according to (85) for prophylactic and/or therapeutic treatment of an inflammatory disease of a mammal.
(89) The medicament according to (85) for prophylactic and/or therapeutic treatment of an autoimmune disease of a mammal.
(90) The medicament according to (85) for prophylactic and/or therapeutic treatment of an allergic disease of a mammal.
(91) The medicament according to (85) for defervescence and/or pain relief of a mammal.
(92) A pharmaceutical composition for prophylactic and/or therapeutic treatment of a condition of living body of a mammal exhibiting an acute or chronic inflammatory reaction, which comprises a prophylactically and/or therapeutically effective amount of a compound represented by the aforementioned formula (I) or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable carrier.
(93) A method for prophylactic and/or therapeutic treatment of a condition of living body of a mammal exhibiting an acute or chronic inflammatory reaction, which comprises administering a prophylactically and/or therapeutically effective amount of a compound represented by the aforementioned formula (I) or a pharmacologically acceptable salt thereof to the mammal.
(94) A compound represented by the following formula (II) : [In the formula, each of C2', C3', C4', C5', and C6'in the aromatic ring (E') represents a ring-constituting carbon atom, any one of them to which Rs'and G does not bind may be replaced with V', V'represents nitrogen atom, or carbon atom substituted with Zx', Zx'has the same meaning as Zx mentioned above, provided that when Zx contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx contains amino group, the amino group may be protected with Rp2, Rs'represents-D-Rx'or-N (Ry') (Rz'), -D-Rx'and-N (Ry') (Rz') have the same meanings as-D-Rx and-N (Ry) (Rz), respectively, provided that when-D-Rx or-N (Ry) (Rz) contains hydroxyl group, the hydroxyl group may be protected with Rpl, when-D-Rx or-N (Ry) (Rz) contains amino group, the amino group may be protected with Rp2, G represents chlorine atom, bromine atom, iodine atom, mesylate group, triflate group, or an arenesulfonate group of which aromatic portion may be substituted with one of Tl or two or more of the same or different T1, and Y'represents a lower alkyl group having 1 to 4 carbon atoms].
(95) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to the ring-constituting carbon atom C2'or C3'in the aromatic ring (E').
(96) The compound according to (94) or (95) mentioned above, wherein, in the formula (II), n is an integer of 2.
(97) The compound according to any one of (94) to (96) mentioned above, wherein, in the formula (II), Rs'is-O-Rx'.
(98) The compound according to any one of (94) to (97) mentioned above, wherein, in the formula (II), Rs'is-D-Rx'or-N (Ry') (Rz'), D is a single bind, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-C (O)-, Rx'is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, Rl is a saturated cyclic alkyl group having 3 to 7 carbon atoms or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms, Rl may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, 4H-chromenyl group, dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group, 1,3-dihydrobenzimidazole group, dihydro-3H-benzoxazole group, or dihydro-3H-benzothiazole group, which binds to A2 at an arbitrary position on the ring, Al is a single bind or an alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group, A2 is a single bind, oxygen atom, sulfur atom, -S (O)-,-S (0) 2-, or-N (R4)- (provided that when A2 is oxygen atom, sulfur atom, -S (O)-,-S (0) 2-, or-N (R4)-, Al is ethylene or trimethylene), R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,-OR5,-N (R6) (R6'),-NHCOR7,-NHS02R8, or-A6-Qa, or they bind to each other to form methylenedioxy group, Qa may be substituted with one of T'or two or more of the same or different T1, and is phenyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, or indazolyl group, which binds to As at an arbitrary position on the ring, R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R5 and R7 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or-A6-Qa, R8 represents a lower alkyl group having 1 to 4 carbon atoms, R6'has the same meaning as R6, or binds to R6 to form a 3-to 6-membered ring of a cycloalkyl group or morpholino group together with the nitrogen atom to which they bind, p in Rc is an integer of 2 to 4, A4 is a single bind or methylene or ethylene, A5 is-C (O)-,-C (S)-, or-S (0) 2-, Rd is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa, Re is an alkyl group having 1 to 8 carbon atoms,-A6-Qa, - (CH2) iRl4,-OR28,-SR28, or-N (R29) (R30), i is an integer of 1 to 3, Ri4 is hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N- dialkylcarbamoyl group having 1 to 4 carbon atoms, R28 is an alkyl group having 1 to 8 carbon atoms or-A6-Qa, R29 is an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or-A6-Qa, R30 represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3-to 6-membered ring of nitrogen-containing cycloalkyl group or morpholino group together with the nitrogen atom to which they bind, Rz'has the same meaning as Rx', or represents-A5-Re, Ry'represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or-A6-Qp, or binds to Rz'to form a saturated or unsaturated nitrogen-containing cyclic substituent having 3 to 7 atoms together with the nitrogen atom to which they bind, when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or -N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2.
(99) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 1 to 3, G binds to C3', Rs'binds to one of the ring-constituting carbon atoms C4', C5', and C6', a ring-constituting carbon atom to which Rs'does not bind among C4', C5', and C6'may be replaced with V', V is nitrogen atom or carbon atom substituted with Zx', Zx'is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-D-Rx'or-N (Ry') (Rz'), D is oxygen atom or sulfur atom, Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2- cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bind, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom, -N (methyl) -, or-N (ethyl)-, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bind or unsubstituted methylene, and A2 is a single bind, one of R2 and R3 is a substituent other than hydrogen atom), p in Rc is an integer of 2 or 3, A4 is a single bind or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4- chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin- 3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group or ethyloxyearbonylamino group, Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4- methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2- yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2- yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2- yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan- 2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7- dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1-(2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4- chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group, or pyrazol-1-yl group together with the nitrogen atom to which they binds, provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2, G is chlorine atom, bromine atom, iodine atom, or triflate group, and Y'is methyl group or ethyl group.
(100) The compound according to any one of (94) to (96) mentioned above, wherein, in the formula (II), Rs'is-N (Ry') (Rz').
(101) The compound according to any one of (94) to (96) mentioned above, wherein, in the formula (II), Rs'is-D-Rx', and D is sulfur atom,-S (O)-,-S (0) 2- or-C (O) -.
(102) The compound according to (94) mentioned above, wherein, in the formula (II), G binds at the position of C2'in the aromatic ring (E'), Rs'binds to one of the ring- constituting carbon atoms C3', C4'and C5', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V'.
(103) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 1 to 3, G binds to C2', Rs'binds to one of the ring-constituting carbon atoms C4', C5', and C6', a ring-constituting carbon atom to which Rs'does not bind among C3', C4', and C5'may be replaced with V', V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N- propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N- diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, provided that when Zx' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-D-Rx'or-N (Ry') (Rz'), D is oxygen atom or sulfur atom, Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2- cyclopentylethyl group, 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bind, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom, -N (methyl) -, or-N (ethyl)-, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bind or unsubstituted methylene, and A2 is a single bind, one of R2 and R3 is a substituent other than hydrogen atom), p in Rc is an integer of 2 or 3, A4 is a single bind or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4- chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin- 3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N-(pyridin-2-yl) amino group, N-(pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4- methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4'chlorophenyl group, indan-2- yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2- yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2- yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan- 2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7- dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4- chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2-13- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorop henyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylearbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group, or pyrazol-1-yl group together with the nitrogen atom, provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2, G is chlorine atom, bromine atom, iodine atom, or triflate group, and Y'is methyl group or ethyl group.
(104) The compound according to (102) or (103) mentioned above, wherein, in the formula (II), n is an integer of 2, Rs'binds to C3'in the aromatic ring (E'), Rs'is-O- Rx', and Y'is methyl group or ethyl group.
(105) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C22 is a ring-constituting carbon atom to which G binds, C3'is a ring- constituting carbon atom to which Rs'binds, C4'may be replaced with V', C5'and C6' are unsubstituted ring-constituting carbon atoms, V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N- dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, l- (3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4'fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorop henyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(106) The compound according to (102) or (103) mentioned above, wherein, in the formula (II), n is an integer of 2, Rs'binds at the position of C4'in the aromatic ring (E'), Rs'is-O-Rx', and Y'is methyl group or ethyl group.
(107) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C2'is a ring-constituting carbon atom to which G binds, C4'is a ring- constituting carbon atom to which Rs'binds, C5'may be replaced with V', C3'and C6' are unsubstituted ring-constituting carbon atoms, V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N- dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, < Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, l- (3'fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(108) The compound according to (102) or (103) mentioned above, wherein, in the formula (II), n is an integer of 2, Rs'binds at the position of C5'in the aromatic ring (E'), Rs'is-O-Rx', and Y'is methyl group or ethyl group.
(109) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C5'or C6'in the aromatic ring (E'), and all of C2', C3', C4', C5'and Cs'in the aromatic ring (E') are not replaced with V'.
(110) The compound according to (109) mentioned above, wherein, in the formula (II), n is an integer of 2, Rs'binds to C5'in the aromatic ring (E'), and Rs'is-0-Rx'.
(111) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'iS carbon atom to which G binds, C5'iS carbon atom to which Rs'binds, C2', C4', and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, l- (3'fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group or 2- (N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(112) The compound according to (109) mentioned above, wherein, in the formula (II), n is an integer of 2, Rs'binds to C6'in the aromatic ring (E'), and Rs'is-O-Rx'.
(113) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), and C6'is V.
(114) The compound according to (113) mentioned above, wherein, in the formula (II), n is an integer of 2, V'is carbon atom substituted with Zx', and Rs'is-O-Rx' (115) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'is carbon atom to which G binds, C4'is a carbon atom to which Rs'binds, C6 is carbon atom substituted with Zx', C2 and C5'are unsubstituted ring- constituting carbon atoms, Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, l' (3'chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl ! ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(116) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5' is nitrogen atom, and C2'and C6'are unsubstituted ring-constituting carbon atoms.
(117) The compound according to (116) mentioned above, wherein, in the formula (II), n is an integer of 2, and Rs'is-O-Rx'.
(118) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'is carbon atom to which G binds, C4'iS carbon atom to which Rs'binds, C5'is nitrogen atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2-(2-fluorophenyl) ethyl group, 2-(3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(119) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5' is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring- constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and D is a single bind, sulfur atom,-S (O) -,-S (0) 2-, or-C (O)-.
(120) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'iS carbon atom to which G binds, C4'is a carbon atom to which Rs'binds, C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2 and C6 are unsubstituted ring-constituting carbon atoms, Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-S-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl ethyl group, 2- [4- (trifluoromethyl) phenyl) ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(121) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5' is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring- constituting carbon atom, C2 and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-N (Ry') (Rz').
(122) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'is carbon atom to which G binds, C4'is a carbon atom to which Rs'binds, C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-N (Ry') (Rz'), Rz'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4'fluorophenylmethyl group, 2'chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorop henyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-l-yl) carbonyl group, (piperidino-l- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry'is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, or morpholino group together with nitrogen atom to which they binds, provided that when-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(123) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'iS carbon atom substituted with-N (Rnl) (Rn2) group (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(124) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'iS carbon atom to which G binds, C4'iS carbon atom to which Rs'binds, C5'is carbon atom substituted with Zx', C2'and c6 are unsubstituted ring- constituting carbon atoms, Zx'is N-methylamino group, N-ethylamino group, N-propylamino group, N- isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, provided that when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(125) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5' is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring- constituting carbon atom, C2'and and C6 are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and Rx'has the same meaning as Rc, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Rc contains amino group, the amino group may be protected with Rp2.
(126) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, C3'iS carbon atom to which G binds, C4'is a carbon atom to which Rs'binds, C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'has the same meaning as Rc, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl, p in Rc is an integer of 2, A4 is a single bind or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4- methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4- chlorophenylmethyl group, or 4-fluorophenylmethyl group, Re is isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N- propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4'methylphenyl) amino group, N' (4'chlorophenyl) amino group, N- (4-fluorophenyl) amino group, pyrrolidino group, piperidino group, or morpholino group, G is bromine atom or iodine atom, and Y'is methyl group or ethyl group.
(127) The compound according to (94) mentioned above, wherein, in the formula (II), G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5' is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring- constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-O-Rx', and Rx'is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra or Rb.
(128) The compound according to (94) mentioned above, wherein, in the formula (II), n is an integer of 2, G binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is carbon atom substituted with nitro group, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(129) A compound represented by the following formula (III) : [In the formula, C2', C3', C4', C5'and C6'in the aromatic ring (E') represent a ring- constituting carbon atom, any one of these atoms to which Rs'and AR'does not bind may be replaced with V', and AR'has the same meaning as that of AR, provided that when AR contains hydroxyl group, the hydroxyl group may be protected with Rp1, and when AR contains amino group, the amino group may be protected with Rp2.].
(130) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to the atom of C2'or C3'in the aromatic ring (E').
(131) The compound according to (129) or (130) mentioned above, wherein, in the formula (III), AR'is a residue of naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-lH-quinoline, benzo [d] isothiazole, IH-indazole, benzo [c] isothiazole, 2H-indazole, imidazo [1, 2- a] pyridine, lH-pyrrolo [2, 3-b] pyridine, isoquinoline, dihydro-2H-isoquinoline, cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole, lH-pyrrolo [3, 2- bjpyridine, benzo [1, 2,5] thiadiazole, 1H-benzotriazole, 1, 3-dihydropyrrolo [2,3- b] pyridine, 1, 3-dihydrobenzimidazole, dihydro-3H-benzoxazole, phthalazine, [1, 8] naphthalidine, [1, 5] naphthalidine, 1H-pyrrolo [3, 2-c] pyridine, lH-pyrrolo [2,3- c] pyridine, lH-pyrazolo [4, 3-b]pyridine, 1H-pyrazolo [4, 3-c]pyridine, 1H-pyrazolo [3,4- c] pyridine, lH-pyrazolo [3, 4-b] pyridine, [1, 2,4] triazolo [4, 3-a] pyridine, thieno [3,2- c] pyridine, thieno [3, 2-b]pyridine, 1H-thieno [3, 2-c] pyrazole, benzo [d] isoxazole, benzo [c] isoxazole, indolizine, 1,3-dihydroindole, lH-pyrazolo [3, 4-d] thiazole, 2H- isoindole, [1, 2,4] triazolo [1, 5-a]pyrimidine, 1H-pyrazolo [3, 4-b]pyrazine, 1H- imidazo [4, 5-b] pyrazine, 7H-purine, or 4H-chromene (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa, when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2).
(132) The compound according to (129) or (130) mentioned above, wherein, in the formula (III), AR'is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, lH-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group, imidazo [l, 2-a] pyridin-7-yl group, 1H-pyrrolo [2,3- b]pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b]pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin- 5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4 ; 3-b] pyridin-5-yl group, lH-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1H- pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b]pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c]pyridin-2-yl group, thieno [3,2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b]pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-blpyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d]isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3,4- d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa, when AR'contains hydroxyl group, the hydroxyl group may be protected with Rp, and whenAR'contains amino group, the amino group may be protected with Rp2).
(133) The compound according to (129) or (130) mentioned above, wherein, in the formula (III), AR'is a residue of naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-lH-quinoline, benzo [d] isothiazole, 1H-indazole, benzo [c] isothiazole, 2H-indazole, imidazol, 2- a] pyridine, lH-pyrrolo [2, 3-b] pyridine, isoquinoline, or dihydro-2H-isoquinoline (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa, when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and whenAR'contains amino group, the amino group may be protected with Rp2).
(134) The compound according to (129) or (130) mentioned above, wherein, in the formula (III), AR'is a residue of cinnoline, quinazoline, quinoxaline, 1H- benzimidazole, benzoxazole, lH-pyrrolo [3, 2-b] pyridine, benzo [1, 2,5] thiadiazole, 1H- benzotriazole, 1, 3-dihydropyrrolo [2, 3-b] pyridine, 1, 3-dihydrobenzimidazole, dihydro-3H-benzoxazole, phthalazine, [1, 8] naphthalidine, [1,5]naphthalidine, 1H- pyrrolo [3, 2-c]pyridine, 1H-pyrrolo [2, 3-c]pyridine, 1H-pyrazolo [4, 3-b] pyridine, 1H- pyrazolo [4, 3-c] pyridine, lH-pyrazolo [3, 4-c] pyridine, lH-pyrazolo [3, 4-b] pyridine, [1, 2,4] triazolo [4, 3-a] pyridine, thieno [3, 2-c] pyridine, thieno [3, 2-b] pyridine, 1H- thieno [3, 2-c] pyrazole, benzo [d] isoxazole, benzo [c] isoxazole, indolizine, 1,3- dihydroindole, 1H-pyrazolo [3, 4-d] thiazole, 2H-isoindole, [1, 2,4] triazolo[1, 5- a] pyrimidine, lH-pyrazolo [3, 4-b] pyrazine, lH-imidazo [4, 5-b] pyrazine, 7H-purine, or 4H-chromene (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa, when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2).
(135) The compound according to any one of (129) to (134) mentioned above, wherein, in the formula (III), Rs'is-O-Rx'.
(136) The compound according to any one of (129) to (135) mentioned above, wherein, in the formula (III), Rs'is-D-Rx'or-N (Ry') (Rz'), D is a single bind, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-C (O)-, Rx'is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, Rl is a saturated cyclic alkyl group having 3 to 7 carbon atoms or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms, Ri may be substituted with one of lower alkyl group having 1 to 4 carbon atoms or two or more of the same or different lower alkyl groups having 1 to 4 carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, 4H-chromenyl group, dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group, 1, 3-dihydrobenzimidazole group, dihydro-3H-benzoxazole group, or dihydro-3H-benzothiazole group, which binds to A2 at an arbitrary position on the ring, Al is a single bind or an alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group may be substituted with, A2 is a single bind, oxygen atom, sulfur atom,-S (O)-,-S (0) 2-, or-N (R4)- (provided that when A2 is oxygen atom, sulfur atom, -S (O)-,-S (O) 2-, or-N (R4)-, Al is ethylene or trimethylene), R2 and R3 independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,-OR5,-N (R6) (R6'),-NHCOR7,-NHSO2R8, or-A6-Qa, or they binds to each other to form methylenedioxy group, Qa is phenyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, or indazolyl group, which may be substituted with one of Tl or two or more of the same or different T1, and binds to A6 at an arbitrary position on the ring, R4 and R6 independently represent hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R5 and R7 independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or-A6-Qa, R8 is a lower alkyl group having 1 to 4 carbon atoms, Rs' has the same meaning as R6, or binds to R6 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen- containing alkyl group or morpholino group, p in Rc is an integer of 2 to 4, A4 is a single bind or methylene or ethylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa, Re is an alkyl group having 1 to 8 carbon atoms,-A6-Qa,- (CH2) iRl4, -OR28,-SR28, or-N (R29) (R30), i is an integer of 1 to 3, R14 is hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N- dialkylcarbamoyl group having 1 to 4 carbon atoms, R28 is an alkyl group having 1 to 8 carbon atoms or-A6-Qa, R29 is an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or-A6-Qa, R3° is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3-to 6- membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing alkyl group or morpholino group, Rz'has the same meaning as Rx', or represents-A5-Re, Ry'is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or-A6-Qp, or binds to Rz'to form a saturated or unsaturated nitrogen-containing cyclic substituent having 3 to 7 atoms, when-D-Rx'or- N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2.
(137) The compound according to any one of (129) to (136) mentioned above, wherein, in the formula (III), Rs'is-N (Ry') (Rz').
(138) The compound according to any one of (129) to (136) mentioned above, wherein, in the formula (III), Rs'is-D-Rx', D is sulfur atom,-S (O)-,-S (0) 2-, or- C (O)-.
(139) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds at the position of C2'in the aromatic ring (E'), and Rs'binds to one of the ring-constituting carbon atoms C3', C4', and C5'.
(140) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C2', Rs'binds to any one of the atoms C3', C4', and C5', a ring- constituting carbon atom to which Rs'does not bind among C3', C4', and C5'may be replaced with V', V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is one kind of group selected from the group consisting of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N- methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N- dimethylsulfamoylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-D-Rx'or-N (Ry') (Rz'), D is oxygen atom or sulfur atom, Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2- cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bind, oxygen atom, sulfur atom, -N (methyl) -, or-N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl) -, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bind or unsubstituted methylene, and A2 is a single bind, one of R2 and R3 is a substituent other than hydrogen atom), p in Rc is an integer of 2 or 3, A4 is a single bind or methylene, A5 is-C (O)-,-C (S) -, or-S (O) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4- chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin- 3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, Rz'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4- methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2- yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2- yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2- yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan- 2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7- dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4- chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2' (4'chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyllethyl group, 2- [3- (trifluoromethyl) phenyll ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-l-yl) carbonyl group, (piperidino-l- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry'is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group or pyrazol-1-yl group together with the nitrogen atom, provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2, AR'is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [blthiophen-4-yl group, benzo [blthiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- 1H-quinolin-5-yl group, benzo [dlisothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, 1H-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [clisothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-alpyridin-7-yl group, 1H-pyrrolo [2, 3- blpyridin-5-yl group, 1H-pyrrolo [2, 3-b]pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group ; quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b]pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2,3- blpyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-blpyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [l, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2- c]pyridin-6-yl group, lH-pyrrolo [3, 2-c]pyridin-4-yl group, lH-pyrrolo [2, 3-c]pyridin- 5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b]pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolol3, 4-clpyridin-5-yl group, 1H- pyrazolo [3, 4-c]pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2, 4] triazolo [4, 3-a]pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c]pyridin-2-yl group, thieno [3, 2- clpyridin-3-yl group, thieno [3, 2-c]pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c]pyrazol-4- yl group, benzo [d]isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [dlisoxazol- 6-yl group, benzo [d]isoxazol-7-yl group, benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4- d]thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a]pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), and Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, provided that when AR' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(141) The compound according to (139) or (140) mentioned above, wherein, in the formula (III), Rs'is-O-Rx', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V'.
(142) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds at the position of C2'in the aromatic ring (E'), Rs'binds to one of the ring-constituting carbon atoms C3', C4', and C5', Rs'is-O-Rx', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V.
(143) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds at the position of C2'in the aromatic ring (E'), Rs'binds to one of the ring-constituting carbon atoms C3', C4', and C5', Rs'is-O-Rx', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V.
(144) The compound according to any one of (139) to (143) mentioned above, wherein, in the formula (III), Rs'binds to C3'.
(145) The compound according to (129) mentioned above, wherein, in the formula (III), C2'is carbon atom to which AR'binds, C3'is carbon atom to which Rs'binds, C4'may be replaced with V', C5'and C6'are unsubstituted ring-constituting carbon atoms, V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N- dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2-(4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyll ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) nap hthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-lH- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d]isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, l-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-IH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b]pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(146) The compound according to (139) to (143) mentioned above, wherein, in the formula (III), Rs'binds to C4'.
(147) The compound according to (129) mentioned above, wherein, in the formula (III), C22 is carbon atom to which AR'binds, C4'iS carbon atom to which Rs'binds, C5'may be replaced with V', C3'and c6 are unsubstituted ring-constituting carbon atoms, V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N- dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, l' (4'chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyll ethyl group, 2- [3- (trifluoromethydphenyll ethyl group, 2- [4- (trifluoromethyl) phenyl ethyl group, 2- [4- (N, N-dimethylamino) phenyll ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-1H- indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(148) The compound according to any one of (139) to (143) mentioned above, wherein, in the formula (III), Rs'binds to C5'.
(149) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to the atom C5'or C6'in the aromatic ring (E').
(150) The compound according to (149) mentioned above, wherein, in the formula (III), Rs'is-O-Rx', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V.
(151) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to the atom C5'or C6'in the aromatic ring (E'), Rs'is-O-Rx', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V.
(152) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to the atom C5'or C6'in the aromatic ring (E'), Rs'is-0-Rx', and all of C2', C3', C4', C5'and C6'in the aromatic ring (E') are not replaced with V.
(153) The compound according to any one of (149) to (152) mentioned above, wherein, in the formula (III), Rs'binds to C5'.
(154) The compound according to (129) mentioned above, wherein, in the formula (III), C3'iS carbon atom to which AR'binds, C5'is carbon atom to which Rs'binds, C2', C4', and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, l- (3'fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo[b]furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo[b]thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, l-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-IH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(155) The compound according to any one of (149) to (152) mentioned above, wherein, in the formula (III), Rs'binds to C6'.
(156) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), and C6'is V'.
(157) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4' in the aromatic ring (E'), Cs'is carbon atom substituted with Zx, C2'and C5'are unsubstituted carbon atoms, and Rs' is -O-Rx'.
(158) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4' in the aromatic ring (E'), C6'is carbon atom substituted with Zx, C2'and C5'are unsubstituted ring- constituting carbon atoms, and Rs'is-O-Rx'.
(159) The compound according to (129) mentioned above, wherein, in the formula (III), C3' is carbon atom to which AR'binds, C4'is a carbon atom to which Rs'binds, C6 is carbon atom substituted with Zx', C2'and C5'are unsubstituted ring- constituting carbon atoms, Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2-[2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyll ethyl group, 2- [4- (N, N-dimethylamino) phenyl ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b]pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, provided that when Ar'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and whenAR'contains amino group, the amino group may be protected with Rp2.
(160) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is nitrogen atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(161) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is nitrogen atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(162) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is nitrogen atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(163) The compound according to (129) mentioned above, wherein, in the formula (III), C3'iS carbon atom to which AR'binds, C4'iS carbon atom to which Rs'binds, C5'is nitrogen atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2-(4-chlorophenyl)ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3-(trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-p henylamino) ethyl group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzotb] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 1- (2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(164) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', D is a single bind, sulfur atom,-S (O)-,-S (0) 2-, or-C (O)-.
(165) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5 iSo a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6 are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and D is a single bind, sulfur atom,-S (O)-,-S (0) 2-, or- C (O)-.
(166) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and D is a single bind, sulfur atom,-S (O) -,-S (O) 2-, or- C (O)-.
(167) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and c62 are unsubstituted ring-constituting carbon atoms, and Rs'is-N (Ry') (Rz').
(168) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5 is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-N (Ry') (Rz').
(169) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-N (Ry') (Rz').
(170) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5 is carbon atom substituted with-N (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2'and C6 are unsubstituted ring- constituting carbon atoms, and Rs'is-O-Rx'.
(171) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'iS carbon atom substituted with-N (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2'and C6'are unsubstituted ring- constituting carbon atoms, and Rs'is-O-Rx'.
(172) The compound according to (123) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'iS carbon atom substituted with-N (Rnl) (Rn2) (provided that one of Rnl and Rn2 is a substituent other than hydrogen atom), C2'and C6' are unsubstituted ring- constituting carbon atoms, and Rs'is-O-Rx'.
(173) The compound according to (129) mentioned above, wherein, in the formula (III), C3'iS carbon atom to which AR'binds, C4' is carbon atom to which Rs'binds, C5' is carbon atom substituted with Zx', C2'and C6 are unsubstituted ring- constituting carbon atoms, Zx'is N-methylamino group, N-ethylamino group, N-propylamino group, N- isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, provided that when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2- fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4- methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2- chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4- methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4- dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, or 2-(N-ethyl-N-phenylamino) ethyl group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) nap hthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2,3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, l-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H- indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH- indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH- indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-1H- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-blpyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-blpyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(174) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2' and C6' are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and Rx'has the same meaning as Rc, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Rc contains amino group, the amino group may be protected with Rp2.
(175) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2' and C6' are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and Rx'has the same meaning as Rc, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Rc contains amino group, the amino group may be protected with Rp2.
(176) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Rs'is-D-Rx', and Rx'has the same meaning as Rc, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Rc contains amino group, the amino group may be protected with Rp2.
(177) The compound according to (129) mentioned above, wherein, in the formula (III), C3'is carbon atom to which AR'binds, C4'is a carbon atom to which Rs'binds, C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, Zx'is fluorine atom, methyl group, hydroxyl group, amino group, N- methylamino group, or N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx' contains amino group, the amino group may be protected with Rp2, Rs'is-O-Rx', Rx'has the same meaning as Rc, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl, p in Rc is an integer of 2, A4 is a single bind or methylene, A5 is-C (O) -,-C (S)-, or-S (0) 2-, Rd is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4- methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4- chlorophenylmethyl group, or 4-fluorophenylmethyl group, Re is isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N- propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4'methylphenyl) amino groups N' (4'chlorophenyl) amino group, N' (4'fluorophenyl) amino group, pyrrolidino group, piperidino group, or morpholino group, and AR'is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6- methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6- aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N- dimethylamino) nap hthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3- methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3- methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H- indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3- dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol- 5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3- methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH- indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-l-propyl-1H- indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-lH- indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2- hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-l- (2-hydroxyethyl)-lH- indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2- methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3- dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3- dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2- dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1- methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol- 5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5- yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo 12, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H- pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2- dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp.
(178) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3', Rs'binds to any one of the atoms C4', C5', and C6', a ring- constituting carbon atom to which Rs' does not bind among C4', C5', and C6 may be replaced with V', V'is nitrogen atom, or carbon atom substituted with Zx', Zx'is fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N- propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N- diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N, N-dimethylsulfamoylamino group, provided that when Zx' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Zx'contains amino group, the amino group may be protected with Rp2, Rs'is-D-Rx'or-N (Ry') (Rz'), D is oxygen atom or sulfur atom, Rx'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2- cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group, A2 is a single bind, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)- (provided that when A2 is oxygen atom, sulfur atom, -N (methyl) -, or-N (ethyl)-, Al is ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q is phenyl group, Al is a single bind or unsubstituted methylene, and A2 is a single bind, one of R2 and R3 is a substituent other than hydrogen atom), p in Rc is an integer of 2 or 3, A4 is a single bind or methylene, A5 is-C (O)-,-C (S) -, or-S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4- chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4- chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin- 3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4- methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N- isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4- chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2- yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group or ethyloxycarbonylamino group, Rz'is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4- methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2- yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2- yl group, 5, 6-dimethylindan-2-yl group, 4-fiuoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2- yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan- 2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7- dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, l- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4- chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5- dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3- chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4- difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4- dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6- dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5- dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3- methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2- methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4- methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3- chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3- chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4- methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4- chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4- fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N- isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxyearbonyl group, N- cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N- cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N- cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4- methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4- chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4- fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4- fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1- yl) carbonyl group, or (morpholino-4-yl) carbonyl group, Ry'is hydrogen atom, methyl group, ethyl group or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol- 1-yl group, or pyrazol-1-yl group together with the nitrogen atom, provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituent-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2, AR'is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4- yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro- lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, lH-indazol-4-yl group, lH-indazol-6-yl group, benzo [clisothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2,3- b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H- isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H- benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H- pyrrolo [3, 2-b] pyridin-5-yl group, lH-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H- benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3- b]pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b]pyridin-4-yl group, 1,3- dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H- benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5- yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3,2- clpyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin- 5-yl group, lH-pyrrolo [2, 3-c] pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, lH-pyrazolo [4, 3-blpyridin-6-yl group, lH-pyrazolo [4, 3-c]pyridin-6-yl group, 1H-pyrazolo [4, 3-c]pyridin-4-yl group, 1H-pyrazolo [3, 4-c]pyridin-5-yl group, 1H- pyrazolo[3,4-c]pyridin-4-yl group, 1H-pyrazolo [3, 4-b]pyridin-5-yl group, 1H- pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2- c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3,2- b] pyridin-6-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4- yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol- 6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5- yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4- d]thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a]pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), and Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2- hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N- dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2- aminoacetylamino group, methylsulfonylamino group, (N, N- dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N- methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, provided that when AR' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when AR'contains amino group, the amino group may be protected with Rp2.
(179) The compound according to (119) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(180) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx, or an unsubstituted ring-constituting carbon atom, C2'and C62 are unsubstituted ring-constituting carbon atoms, and D is oxygen atom.
(181) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C-9'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is a ring-constituting carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(182) The compound according to (129) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'iS carbon atom substituted with nitro group, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(183) The compound according to (131) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is carbon atom substituted with nitro group, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(184) The compound according to (132) mentioned above, wherein, in the formula (III), AR'binds to C3'in the aromatic ring (E'), Rs'binds to C4'in the aromatic ring (E'), C5'is carbon atom substituted with nitro group, C2'and C6'are unsubstituted ring-constituting carbon atoms, and Rs'is-O-Rx'.
(185) An agent for prophylactic and/or therapeutic treatment of fibrosis, which contains a type 4 PLA2 inhibitor as an active ingredient.
(186) An agent for prophylactic and/or therapeutic treatment of pulmonary fibrosis, which contains a type 4 PLA2 inhibitor as an active ingredient..
(187) The prophylactic and/or therapeutic agent according to (186), wherein the pulmonary fibrosis is drug-induced pulmonary fibrosis.
(188) The prophylactic and/or therapeutic agent according to (187), wherein the drug-induced pulmonary fibrosis is a disease induced by one or more kinds of medicaments among methotrexate, sodium aurothiomalate, auranofin, D- penicillamine, bucillamine, actarit, salazosulfapyridine, cyclophosphamide, Taxol, etoposide, cisplatin, vincristine, vinblastine, irinotecan, gefitinib, and bleomycin.
(189) The prophylactic and/or therapeutic agent according to (187), wherein the drug-induced pulmonary fibrosis is a disease induced by one or more kinds of medicaments among methotrexate and bleomycin.
(190) The prophylactic and/or therapeutic agent according to (186), wherein the type 4 PLA2 inhibitor is a compound represented by the formula (I) or a pharmacologically acceptable salt thereof.
(191) The prophylactic and/or therapeutic agent according to (186), wherein the type 4 PLA2 inhibitor is an inhibitor selected from the group consisting of 4- (1- benzhydryl-6-chloro-lH-indol-3-ylmethyl)-3-methoxybenzoic acid, 4- {4- [2- (2- [bis (4- chlorophenyl) methoxy] ethylsulfonyl) ethoxy] phenyl}-1, 1, 1-trifluoro-2-butanone, N- {1- [2- (2, 4-difluorobenzoyl) benzoyl]-4-tritylsulfanylpyrrolidin-2-ylmethyl}-4- (2, 4- dioxothiazolidin-5-ylidenemethyl) benzoic acid amide, 4-methyl-2-oxo-5- (5, 6,7, 8- tetrahydronaphthalen-2-yl) oxazolidine-3-carbonxylic acid (6- methoxytetrahydropyran-2-yl) amide, 4-methyl-2-oxo-5- (4- methylphenyl) thiazolidine-3-carbonxylic acid (tetrahydropyran-2-yl) amide, 4- [3- (4- decyloxyphenyloxy)-2-oxopropyloxyabenzoic acid, and 1- {2- [4- (carboxymethyl) phenoxy] ethyl}-3-dodecanoylindole-2-carbonxylic acid.
The compound (I) of the present invention or a pharmaceutically acceptable salt thereof has an action of suppressing the production of both of prostaglandins and leukotrienes, and said compound has characteristic features that, when administered to a human or animal, the compound exerts superior prophylactic and/or therapeutic effect on diseases or pathological conditions in which a prostaglandin and/or leukotriene is involved, and the compound has extremely low toxicity. The compounds (II) and (III) of the present invention are synthetic intermediates useful for the production of the compound (I) of the present invention.
Furthermore, it was confirmed that a type 4 PLA2 inhibitor is useful as a prophylactic and/or therapeutic agent for fibrosis, in particular, pulmonary fibrosis, especially drug-induced pulmonary fibrosis, which was induced as a side effect of a medicament.
Best Mode for Carrying out the Invention In the present specification, carbon atom may sometimes be represented simply by"C", hydrogen atom by"H", oxygen atom by"O", sulfur atom by"S", and nitrogen atom by"N".
Examples of Link in the aforementioned general formula (I) include a saturated straight hydrocarbon chain having 1 to 3 carbon atoms or an unsaturated straight hydrocarbon chain having 2 or 3 carbon atoms. In the present invention, the straight chain of the saturated straight hydrocarbon chain is preferably unsubstituted. The straight chain of the unsaturated straight hydrocarbon chain is also preferably unsubstituted. As the saturated straight hydrocarbon chain, - (CH2) n- is preferred. Symbol n is an integer of 1 to 3. When n is 1,2 or 3, the desired action is most characteristically exhibited. Methylene where n is 1, ethylene where n is 2 and trimethylene where n is 3 are preferred, and ethylene where n is 2 is particularly preferred.
The unsaturated hydrocarbon chain having 2 or 3 carbon atoms means a hydrocarbon chain which contains an unsaturated bond as a double bond or a triple bond among the carbon-carbon bonds. As the unsaturated hydrocarbon chain, an unsaturated hydrocarbon chain containing a double bond is preferred. When the chain contains one or more double bonds, the number of the double bond may preferably one. Specific examples include ethenylene which has two carbon atoms and contains one double bond, as well as ethynylene which has two carbon atoms and contains one triple bond, propen-3-yl which has three carbon atoms and contains one double bond, and propyn-3-yl which has three carbon atoms and contains one triple bond.
C2, C3, C4, C5 and C6 in the aromatic ring (E) in the formula (I) each represent a ring-constituting carbon atom. The ring-constituting carbon atoms form the aromatic ring (E), and accordingly, they are represented as C or CH.
Among them, any one of ring-constituting carbon atoms to which Rs or Ar does not bind may be replaced with V. The aforementioned expression"to be replaced with" means that any one of the ring-constituting carbon atoms C2, C3, C4, C5 and C6 is replaced with V, and thus V may sometimes be a ring-constituting component. Rs and AR each bind to any of the ring-constituting carbon atoms C2, C3, C4, C5 or C6 in the aromatic ring (E), and this means that, for example, when AR binds to C2, Rs binds to any of the ring-constituting carbon atoms C3, C4, C5 and C6, when AR binds to C3, Rs binds to any of the ring-constituting carbon atoms C2, C4, C5 and C6, and when AR bind to C4, Rs binds to the ring-constituting carbon atom C2 or C3.
Preferred examples of these combinations of substitution positions include a compound wherein AR binds to C2, and Rs binds to any of the atoms C3, C4, and C5, and particularly preferred examples include a compound wherein AR binds to C2, and Rs binds to C3 or C4. Preferred examples also include a compound wherein AR binds to C3, and Rs binds to any of the atoms C4, C5, and C6, and particularly preferred examples also include a compound wherein AR binds to C3, and Rs binds to the atom C4 or C5. A still more preferred example is a compound wherein AR binds to C3, and Rs binds to C4.
One of the atoms C2, C3, C4, C5 and C6 to which Rs and AR do not bind may be replaced with V. For example, when AR binds to C2, and Rs binds to C3, one of the ring-constituting carbon atoms C4, C5, and C6 may be replaced with V. As another example, it is meant that when AR binds to C3, and Rs binds to C4, one of the atoms C2, C5, and C6 may be replaced with V. Among them combinations and other combinations, preferred examples are a compound wherein AR binds to C2, Rs binds to C3, and C4 is replaced with V ; a compound wherein AR binds to C2, Rs binds to C4, and C5 is replaced with V a compound wherein AR binds to C2, Rs binds to C5, and C4 is replaced with V ; a compound wherein AR binds to C3, Rs binds to C4, and C5 is replaced with V ; a compound wherein AR binds to C3, Rs binds to C4, and C6 is replaced with V ; a compound wherein AR binds to C3, Rs binds to C5, and C4 is replaced with V ; a compound wherein AR binds to C3, Rs binds to C6, and C5 is replaced with V, and the like. Furthermore, particularly preferred examples include a compound wherein AR binds to C3, Rs binds to C4, and C5 is replaced with V and a compound wherein AR binds to C3, Rs binds to C4, and C6 is replaced with V, and an particularly preferred example is a compound wherein AR binds to C3, Rs binds to C4, and C5 is replaced with V.
V represents nitrogen atom, or carbon atom substituted with Zx. Namely, when V represent nitrogen atom, the aromatic ring (E) in the formula (I) represents a pyridine ring. When V represent carbon atom substituted with Zx, the aromatic ring (E) is a benzene ring having Zx. Both of the compounds are particularly preferred. Furthermore, a compound wherein AR binds to C3, Rs binds to C4, C5 is V replaced with V, and this V represents nitrogen atom is particularly preferred.
Zx is defined as a linear or branched saturated alkyl group having 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, nitro group,-OR9, or -N (Rnl) (Rn2). Among them, fluorine atom, chlorine atom, bromine atom, and nitro group are preferred examples, and fluorine atom is particularly preferred.
As for Zx, examples of the linear or branched saturated alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group and the like, and among them, methyl group is particularly preferred.
R9 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or-A6-Qp. Among them, hydrogen atom is a particularly preferred example.
Preferred examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and methyl group is particularly preferred.
As in-A6-Qp represents a single bond or methylene, and Qp represents a phenyl group which may be substituted with one of T1 or two or more of the same or different T1. The substituent T1 is a linear or branched saturated alkyl group having 1 to 4 carbon atoms, hydroxyl group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, nitro group, an alkoxy group having 1 to 4 carbon atoms, or a mono-or dialkylamino group having 1 to 4 carbon atoms. Specific examples of-A6-Qp include phenyl group, methylphenyl group, chlorophenyl group, benzyl group, methylbenzyl group, chlorobenzyl group, dichlorobenzyl group, fluorobenzyl group, trifluoromethylbenzyl group, nitrobenzyl group, methoxyphenyl group, N-methylaminobenzyl group, N, N-dimethylaminobenzyl group, and the like.
Preferred examples of-OR9 include hydroxyl group, methoxy group, and the like, and hydroxyl group is particularly preferred.
Rnl represents hydrogen atom or a linear or branched saturated alkyl group having 1 to 4 carbon atoms, and hydrogen atom is particularly preferred. Examples of the linear or branched saturated alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, or t-butyl group, and the like. Among them, methyl group, ethyl group, propyl group, isopropyl group, and the like are preferred examples, and methyl group is particularly preferred.
Rn2 has the same meaning as Rnl, or represents a-COR23 group or a-SO2R24 group, or binds to Rnl to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group.
R23 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms,-O-A6-Qp, or-N (R25) (R26).
R25 represents hydrogen atom, or a linear or branched saturated alkyl group having 1 to 4 carbon atoms. R26 has the same meaning as R25, or binds to R25 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogen-containing cycloalkyl group or morpholino group. Examples of the compound wherein R26"binds to R25 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to represent a saturated nitrogen-containing cycloalkyl group or morpholino group"include, for example, a compound wherein a cyclic aminoalkyl group containing nitrogen atom such as pyrrolidino group, piperazino group and morpholino group is formed.
Specific examples of-COR23 include formyl group, acetyl group, t-butyloxycarbonyl group, phenyloxycarbonyl group, benzyloxycarbonyl group, carbamoyl group, N'methylcarbamoyl group, N, N-dimethylcarbamoyl group, piperidine-l-carbonyl group, morpholine-4-carbonyl group, and the like, and preferred examples include formyl group, acetyl group, carbamoyl group, and the like. In the aforementioned formulas, as represented by As and Qp, for example, the same symbols may sometimes be used simultaneously at different positions.
These symbols are used to mean the same class of groups of substituents. However, because each substituent is independently chosen from each other, the same symbols do not mean that an identical substituent should be necessarily chosen, and as a result, selection of the same or different kind of substituent is not prohibited.
R24 represents a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono-or dialkylamino group having 1 to 4 carbon atoms. Specific examples of -SO2R24 include mesyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, and the like, and preferred examples include mesyl group, N, N-dimethylsulfamoyl group, and the like.
Specific examples of-N (Rnl) (Rn2) include amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, piperidino group, pyrrolidino group, morpholino group, formylamino group, acetylamino group, t-butyloxycarbonylamino group, phenyloxycarbonylamino group, benzyloxycarbonylamino group, carbamoylamino group, N-methylcarbamoylamino group, N, N-dimethylcarbamoylamino group, piperidine-1-carbonylamino group, morpholine-4-carbonylamino group, mesylamino group, sulfamoylamino group, N-methylsulfamoylamino group, N, N-dimethylsulfamoylamino group, and the like.
Among them, preferred examples include amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, N, N-dimethylsulfamoylamino group, and the like, and amino group, N-methylamino group, and N, N-dimethylamino group are particularly preferred.
Therefore, preferred examples of Zx include fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, N, N-dimethylsulfamoylamino group, and the like, and particularly preferred examples include fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, N, N-dimethylamino group, and the like.
In the formula (I), Rs is defined to represent-D-Rx or-N (Ry) (Rz).
D is defined to represent a single bond, oxygen atom, sulfur atom,-S (O) -, -S (0) 2-, or-C (O)-. Among them, oxygen atom and sulfur atom are preferred, and oxygen atom is particularly preferred. Another preferred examples include the compounds wherein D represent a single bond.
Rx represents a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or represents Ra, Rb, or Rc mentioned above.
As for Rx, examples of the linear or branched saturated alkyl group having 3 to 8 carbon atoms include, for example, propyl group, isopropyl group, butyl group, isobutyl group, 1-methylpropyl group, t-butyl group, pentyl group, isopentyl group, 2-methylbutyl group, 2,2-dimethylpropyl group, hexyl group, 4-methylpentyl group, 2, 3-dimethylbutyl group, 2-ethylbutyl group, heptyl group, octyl group, and the like, and butyl group, isobutyl group, and 2-ethylbutyl group are particularly preferred.
As for Rx, Ru ouf Ra is defined to be a saturated cyclic alkyl group having 3 to 7 carbon atoms substituted with a lower alkyl group having 1 to 4 carbon atoms or an unsubstituted saturated cyclic alkyl group having 3 to 7 carbon atoms, or a condensed saturated cyclic alkyl group having 6 to 8 carbon atoms substituted with a lower alkyl group having 1 to 4 carbon atoms or an unsubstituted condensed saturated cyclic alkyl group having 6 to 8 carbon atoms. As for R1, examples of the saturated cyclic alkyl group having 3 to 7 carbon atoms include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and the like, and cyclopentyl group, cyclohexyl group, and cycloheptyl group are particularly preferred. As for RI, examples of the condensed saturated cyclic alkyl group having 6 to 8 carbon atoms group include bicyclo [2,2, heptyl group, bicyclo [2,2, 2] octyl group, and the like.
Examples of the lower alkyl group having 1 to 4 carbon atoms substituting on R1 include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like. Examples of Rl substituted with a lower alkyl group having 1 to 4 carbon atoms include methylcyclopentyl group, methylcyclohexyl group, methylbicyclo [2,2, heptyl group, and the like.
Symbol k is defined to be 0 or an integer of 1 to 3. A single bond where k is 0, methylene where k is 1, and ethylene where k is 2 are preferred, and a bond where k is 0, and methylene where k is 1 are particularly preferred.
Examples of Ra include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethyl group, 3-cyclohexylpropyl group, 2-methylcyclopentyl group, 3'methylcyclopentyl group, 3,4-dimethylcyclopentyl group, 4-methylcyclohexyl group, 4, 4-dimethylcyclohexyl group, 4-ethylcyclohexyl group, 4-methylcyclohexylmethyl group, bicyclo [2,2, 1] heptane-2-methyl group, bicyclo [2,2, 2] octane-2-methyl group, 3-methylbicyclo [2,2, 1]heptane-2-methyl group, bicyclo [2, 2, 1] hept-1-ylmethyl group, bicyclo [2,2, 2] oct-1-ylmethyl group, and the like. Cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethyl group are preferred, and cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group are particularly preferred.
As for Rx, A2 in Rb is defined to be a single bond, oxygen atom, sulfur atom, -S(O)-, -S(O)2-, or-N (R4)-. R4 is defined to be a lower alkyl group having 1 to 4 carbon atoms. Preferred examples are methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and methyl group and ethyl group are particularly preferred examples. Therefore, particularly preferred examples of A2 include a single bond, oxygen atom, sulfur atom, -N (methyl) -, and-N (ethyl)-.
Al is defined to be a single bond or an alkylene (a) having 1 to 3 carbon atoms, i. e. , methylene, ethylene or trimethylene. However, when A2 represents oxygen atom, sulfur atom,-S (O)-,-S (0) 2-or-N (R4)-, Al is ethylene or trimethylene.
Further, the alkylene (a) may be substituted with a lower alkyl group having 1 to 4 carbon atoms or phenyl group. Examples of the lower alkyl group having 1 to 4 carbon atoms for the above compound include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and methyl group, and ethyl group are preferred examples. Specific examples of Al include methylene, methylmethylene, ethylmethylene, phenylmethylene, ethylene, methylethylene, dimethylethylene, ethylethylene, phenylethylene, trimethylene, methyltrimethylene, and the like. Among them, when A2 represents a single bond, Al is most preferably a single bond, or methylene, methylmethylene, or ethylene.
Further, when A2 represents oxygen atom, sulfur atom,-S (O)-,-S (0) 2-or-N (R4)-, A is most preferably ethylene.
Q in Rb is defined to be a residue of a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or heterocyclic ring (q), and the heterocyclic ring (q) means a ring containing 1 to 4 the same or different ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom. The term"residue"means a monovalent group formed by eliminating hydrogen atom bonding to a ring-constituting atom. The residue of monocyclic carbon ring or heterocyclic ring is a partially unsaturated or completely unsaturated substituent having 5 to 7 atoms, and examples include, for example, phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, and the like. Among them, phenyl group, thienyl group, furyl group, pyridyl group, and oxazolyl group are preferred examples, and phenyl group is particularly preferred.
The condensed bicyclic carbon ring or heterocyclic ring is a partially unsaturated or completely unsaturated ring having 8 to 11 atoms, and examples of residue thereof include, for example, naphthyl group, tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, 4H-chromenyl group, dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group, 1,3-dihydrobenzimidazole group, dihydro-3H-benzoxazole group, dihydro-3H-benzothiazole group, and the like. Among them, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group are preferred examples, and indanyl group is one of particularly preferred examples.
Q binds to A2 at an arbitrary position on the ring. Preferred examples of Q with indication of bonding position include phenyl group, 2-or 3-thienyl group, 2-or 3-furyl group, 2-, 3-or 4-pyridyl group, 2-, 4-or 5-oxazolyl group, 1-or 2-naphthyl group, 1-, 2-, 5-or 6-tetrahydronaphthyl group, indan-1-yl group, indan-2-yl group, indan-4-yl group, indan-5-yl group, 1-, 2-, 3-, 4-, 5-, 6-, or 7-indolyl group, 2-, 5-or 6-dihydrobenzodioxyl group, and the like. Among them, phenyl group, and indan-2-yl group are particularly preferred.
In Rb, R2 and R3 are defined to be substituents of Q, and independently represent hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group,-OR5,-N (R6) (R6'),-NHCOR7,-NHS02R8, or-A6-Qa, or bind to each other to represent methylenedioxy group.
Examples of the linear or branched saturated alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and methyl group is particularly preferred.
R6 in-N (Rs) (R6') represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. R6'has the same meaning as R6, or binds to R6 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group. Therefore, specific examples of-N (R6) (R6') include amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N'diethylamino group, piperidino group, pyrrolidino group, morpholino group, and the like. N, N-Dimethylamino group, piperidino group, morpholino group, and the like are preferred examples, and N, N-dimethylamino group is a particularly preferred example.
R5 and R7 are defined to independently represent hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or a-A6-Qa group. Examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and among them, methyl group is a preferred example.
A6 in-A6-Qa has the same meaning as that defined above. Qa is defined to be a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or heterocyclic ring (qa), and the heterocyclic ring (qa) means a substituent containing 1 to 4 the same or different ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom.
The monocyclic carbon ring or heterocyclic ring is a partially unsaturated or completely unsaturated ring having 5 to 7 atoms, and examples of residue thereof include, for example, phenyl group, thienyl group, furyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, and the like. The condensed bicyclic carbon ring or heterocyclic ring is a partially unsaturated or completely unsaturated ring having 8 to 11 atoms, and examples of residue thereof include, for example, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, and the like.
Qa binds to A6 at an arbitrary position on the ring. Further, Qa may be substituted with two or more of the same or different TI. Tl has the same meaning as defined above.
Specific examples of-A6-Qa include phenyl group, methylphenyl group, chlorophenyl group, benzyl group, methylbenzyl group, chlorobenzyl group, dichlorobenzyl group, fluorobenzyl group, trifluoromethylbenzyl group, nitrobenzyl group, methoxyphenyl group, N-methylaminobenzyl group, N, N-dimethylaminobenzyl group, furyl group, thienyl group, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, naphthyl group, indanyl group, indenyl group, quinolyl group, isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, indazolyl group, and the like.
R3 each defined to be a lower alkyl group having 1 to 4 carbon atoms, and examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like.
Therefore, preferred examples of R2 and R3 include hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, and methylsulfonylamino group, and hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, and dimethylamino group are particularly preferred. When Q represents phenyl group, A1 represents a single bond, or unsubstituted methylene, and A2 represents a single bond, at least one of R2 and R3 preferably represents a substituent other than hydrogen atom.
Particularly preferred examples of Rb include 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2-[2-(trifluoromethyl) phenyllethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, and the like.
Symbol p in Rc is defined to be an integer of 2 to 4. Ethylene where p is 2, and trimethylene where p is 3 are preferred, and ethylene where p is 2 is particularly preferred. A4 represents a single bond, or represents methylene or ethylene, and a single bond and methylene are particularly preferred. A5 represents-C (O)-,-C (S) -, or-S (0) 2-, and all of them are preferred. Rd represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or group Qa. Re represents an alkyl group having 1 to 8 carbon atoms, a-As-Qa group, a- (CH2) iRl4 group, a-OR28 group, a-SR28 group, or a-N (R29) (R3Q) group. The group Qa and -A6-Qa have the same meanings as defined above.
The alkyl group having 1 to 8 carbon atoms is a linear or branched saturated alkyl group or a linear or branched partially unsaturated alkyl group, or an alkyl group which may contain a cycloalkyl group having 3 to 7 carbon atoms, and examples include, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, isopentyl group, 2-methylbutyl group, 2, 2-dimethylpropyl group, hexyl group, 4-methylpentyl group, 2, 3-dimethylbutyl group, 2-ethylbutyl group, heptyl group, octyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, 3,4-dimethylcyclopentyl group, 4-methylcyclohexyl group, 4, 4-dimethylcyclohexyl group, 4-ethylcyclohexyl group, 4-methylcyclohexylmethyl group, and the like.
Symbol i in-(CH2) iRl4 represents an integer of 1 to 3, and R14 represents hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxyl group, or an N, N-dialkylcarbamoyl group having 1 to 4 carbon atoms. Examples of the alkoxy group having 1 to 4 carbon atoms include methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butoxy group, isobutyloxy group, t-butyloxy group, and the like. Examples of the N, N-dialkylcarbamoyl group having 1 to 4 carbon atoms include N, N-dimethylcarbamoyl group, N, N-diethylcarbamoyl group, and the like.
R28 in-OR28 or-SR28 represents an alkyl group having 1 to 8 carbon atoms, or-A6-Qa, and these have the same meanings as defined above.
R29 in-N (R29) (R30) represents an alkyl group having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or-A6-Qa. Among them, the alkyl group having 1 to 8 carbon atoms and-A6-Qa have the same meanings as those defined above. Examples of the alkoxycarbonyl group having 1 to 4 carbon atoms include methyloxycarbonyl group, ethyloxycarbonyl group, propyloxycarbonyl group, isopropyloxyearbonyl group, butyloxycarbonyl group, isobutyloxycarbonyl group, t'butyloxycarbonyl group, and the like. R30 represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, or binds to R29 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group. The lower alkyl group having 1 to 4 carbon atoms has the same meaning as defined above. Examples of the compound where"R30 binds to R29 to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group"include, for example, a compound wherein a cyclic aminoalkyl group containing nitrogen atom such as pyrrolidino group, piperazino group, and morpholino group is formed.
Preferred examples of Rd include hydrogen atom as well as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorobenzyl group, 4-fluorobenzyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, and the like.
Particularly preferred examples of Rd include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, and the like.
Preferred examples of substituted-A4-Rd include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isoamyl group, cyclopropyl group, cyclopropylmethyl group, 2- (cyclopropyl) ethyl group, cyclopentyl group, cyclopentylmethyl group, 2- (cyclopentyl) ethyl group, cyclohexyl group, cyclohexylmethyl group, 2- (cyclohexyl) ethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, 2- (4'chlorophenyl) ethyl group, 2' (4'fluorophenyl) ethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, (pyridin-2-yl) methyl group, (pyridin-3-yl) methyl group, (pyridin-4-yl) methyl group, and the like.
Particularly preferred examples of substituted-A4-Rd include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isoamyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, 2' (4'chlorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, and the like.
Preferred examples of Re include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, methylthioxo group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, ethyloxycarbonylamino group, and the like.
Particularly preferred examples of Re include isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, pyrrolidino group, piperidino group, morpholino group, and the like.
Preferred examples of-A5-Re include acetyl group, thioacetyl group, methanesulfonyl group, propionyl group, ethylthiocarbonyl group, butyryl group, propylthiocarbonyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, phenylmethylcarbonyl group, 4-methylphenylmethylcarbonyl group, 4-chlorophenylmethylcarbonyl group, 4-fluorophenylmethylcarbonyl group, (pyridin-2-yl) carbonyl group, (pyridin-2-yl) thiocarbonyl group, (pyridin-3-yl) carbonyl group, (pyridin-4-yl) carbonyl group, (furan-2-yl) carbonyl group, (thiophen-2-yl) carbonyl group, methyloxycarbonyl group, methylsulfanylcarbonyl group, methyloxythiocarbonyl group, methyloxycarbonylaminocarbonyl group, carbamoyl group, N-methylcarbamoyl group, N-methylthiocarbamoyl group, N, N-dimethylcarbamoyl group, N, N-dimethylthiocarbamoyl group, N, N-dimethylsulfamoyl group, ethyloxycarbonyl group, ethyloxycarbonylaminocarbonyl group, N-ethylcarbamoyl group, N-ethylthiocarbamoyl group, N, N-diethylcarbamoyl group, N, N-diethylthiocarbamoyl group, N, N-diethylsulfamoyl group, propyloxycarbonyl group, N-propylcarbamoyl group, N-propylthiocarbamoyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, phenylmethyloxycarbonyl group, 4-methylphenylmethyloxycarbonyl group, 4-chlorophenylmethyloxycarbonyl group, 4-fluorophenylmethyloxycarbonyl group, N- (pyridin-2-yl) carbamoyl group, N- (pyridin-2-yl) thiocarbamoyl group, N- (pyridin-3-yl) carbamoyl group, N- (pyridin-3-yl) thiocarbamoyl group, N- (pyridin-4-yl) carbamoyl group, N- (pyridin-4-yl) thiocarbamoyl group, N- (furan-2-yl) carbamoyl group, N- (thiophen-2-yl) carbamoyl group, (pyrrolidino-l-yl) carbonyl group, (piperidino-1-yl) carbonyl group, (morpholino-4-yl) carbonyl group, and the like.
Particularly preferred examples of-A5-Re include isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1-yl) carbonyl group, (morpholino-4-yl) carbonyl group, and the like.
Specific examples of Rc include 2-(N-isobutyryl-N-methylamino) ethyl group, 2- (N-ethyl-N-isobutyrylamino) ethyl group, 2- (N-isobutyryl-N-propylamino) ethyl group, 2- (N-isobutyryl-N-isopropylamino) ethyl group, 2- (N-butyl-N-isobutyrylamino) ethyl group, 2- (N-isobutyl-N-isobutyrylamino) ethyl group, 2- (N-cyclopropyl-N-isobutyrylamino) ethyl group, 2- (N-cyclop entyl-N-isobutyrylamino) ethyl group, 2- (N-cyclop entylmethyl-N-isobutyrylamino) ethyl group, 2- (N-cyclohexyl-N-isobutyrylamino) ethyl group, 2- (N-cyclohexylmethyl-N-isobutyrylamino) ethyl group, 2- (N-isobutyryl-N-phenylamino) ethyl group, 2- [N-isobutyryl-N- (4-methylphenyl) amino] ethyl group, 2- [N- (4-chlorophenyl)-N-isobutyrylamino] ethyl group, 2- [N- (4-fluorophenyl)-N-isobutyrylamino] ethyl group, 2- (N-benzyl-N-isobutyrylamino) ethyl group, 2- [N- (4-chlorophenylmethyl)-N-isobutyrylamino] ethyl group, 2- [N- (4-fluorophenylmethyl)-N-isobutyrylamino] ethyl group, 2- [N- [2- ( 4chlorophenyl) ethyl]-N-isobutyrylamino] ethyl group, 2- [N- [2- (4-fluorophenyl) ethyl]-N-isobutyrylamino] ethyl group, 2-(N-isobutylthiocarbonyl-N-methylamino) ethyl group, 2-(N-isobutylthiocarbonyl-N-isopropylamino) ethyl group, 2-(N-butyl-N-isobutylthiocarbonylamino) ethyl group, 2-(N-isobutyl-N-isobutylthiocarbonylamino) ethyl group, 2- (N-cyclopentyl-N-isobutylthiocarbonylamino) ethyl group, 2- (N-cyclop entylmethyl-N-isobutylthiocarbonylamino) ethyl group, 2- (N-isobutylthiocarbonyl-N-phenylamino) ethyl group, 2-(N-benzyl-N-isobutylthiocarbonylamino) ethyl group, 2- [N- (4-fluorophenylmethyl)-N-isobutylthiocarbonylamino] ethyl group, 2- (N-methyl-N-pivaloylamino) ethyl group, 2- (N-isopropyl-N-pivaloylamino) ethyl group, 2- (N-butyl-N-pivaloylamino) ethyl group, 2- (N-isobutyl-N-pivaloylamino) ethyl group, 2- (N-cyclohexyl-N-pivaloylamino) ethyl group, 2- (N-cyclohexylmethyl-N-pivaloylamino) ethyl group, 2- (N-phenyl-N-pivaloylamino) ethyl group, 2- (N-benzyl-N-pivaloylamino) ethyl group, 2- (N-cyclopentylcarbonyl-N-methylamino) ethyl group, 2- (N-butyl-N-cyclopentylcarbonylamino) ethyl group, 2-(N-cyclopentylcarbonyl-N-isobutylamino) ethyl group, 2- (N-cyclopentylcarbonyl-N-cyclopentylmethylamino) ethyl group, 2- (N-cyclopentylcarbonyl-N-phenylamino) ethyl group, 2- [N-cyclop entylcarbonyl-N- (4-fluorophenyl) amino] ethyl group, 2- (N-benzyl-N-cyclopentylcarbonylamino) ethyl group, 2- [N-cyclopentylcarbonyl-N-(4-fluorophenylmethyl) amino] ethyl group, 2- (N-methyl-N-phenylsulfonylamino) ethyl group, 2-(N-ethyl-N-phenylsulfonylamino) ethyl group, 2-(N-phenylsulfonyl-N-propylamino) ethyl group, 2- (N-isopropyl-N-phenylsulfonylamino) ethyl group, 2-(N-butyl-N-phenylsulfonylamino) ethyl group, 2-(N-isobutyl-N-phenylsulfonylamino) ethyl group, 2-(N-cyclopropyl-N-phenylsulfonylamino) ethyl group, 2- (N-cyclopentyl-N-phenylsulfonylamino) ethyl group, 2- (N-cyclopentylmethyl-N-phenylsulfonylamino) ethyl group, 2- (N-cyclohexyl-N-p henylsulfonylamino) ethyl group, 2-(N-cyclohexylmethyl-N-phenylsulfonylamino) ethyl group, 2- (N-phenyl-N-phenylsulfonylamino) ethyl group, 2- [N- (4-fluorophenyl)-N-phenylsulfonylamino] ethyl group, 2- (N-benzyl-N-phenylsulfonylamino) ethyl group, 2- [N- (N-butylcarbamoyl)-N-methylamino] ethyl group, 2- [N-butyl-N- (N-butylcarbamoyl) amino] ethyl group, 2- [N- (N-butylcarbamoyl)-N-isobutylamino] ethyl group, 2- [N- (N-butylcarbamoyl)-N-cyclopentylamino] ethyl group, 2- [N- (N-butylcarbamoyl)-N-cyclohexylmethylamino] ethyl group, 2- [N- (N-butylcarbamoyl)-N-phenylamino] ethyl group, 2-{N- (N-butylcarbamoyl) -N- (4-fluorophenyl) amino} ethyl group, 2- [N-benzyl-N- (N-butylcarbamoyl) amino] ethyl group, 2- {N- (N-butylcarbamoyl) -N- (4-fluorophenylmethyl) amino} ethyl group, 2-{N- (N-butylcarbamoyl)-N- [2- (4-fluorophenyl) ethyl] amino} ethyl group, 2-[N-(N-isopropylthiocarbamoyl)-N-methylamino] ethyl group, 2-[N-butyl-N-(N-isopropylthiocarbamoyl) amino] ethyl group, 2- [N-isobutyl-N- (N-isopropylthiocarbamoyl) amino] ethyl group, 2- [N-cyclopentyl-N-(N-isopropylthiocarbamoyl) amino] ethyl group, 2- [N-cyclohexylmethyl-N- (N-isopropylthiocarbamoyl) amino] ethyl group, 2- [N- (N-isopropylthiocarbamoyl)-N-phenylamino] ethyl group, 2-{N- (4-fluorophenyl) -N- (N-isopropylthiocarbamoyl) amino} ethyl group, 2- [N-benzyl-N- (N-isopropylthiocarbamoyl) amino] ethyl group, 2- (N-isobutyloxycarbonyl-N-methylamino) ethyl group, 2- (N-butyl-N-isobutyloxycarbonylamino) ethyl group, 2- (N-isobutyl-N-isobutyloxycarbonylamino) ethyl group, 2- (N-cyclopentyl-N-isobutyloxycarbonylamino) ethyl group, 2-(N-cyclohexylmethyl-N-isobutyloxycarbonylamino) ethyl group, 2- (N-isobutyloxycarbonyl-N-phenylamino) ethyl group, 2- [N- (4-fluorophenyl)-N-isobutyloxycarbonylamino] ethyl group, 2- (N-benzyl-N-isobutyloxycarbonylamino) ethyl group, 2- [N- (N-cyclopentylcarbamoyl)-N-methylamino] ethyl group, 2- [N-butyl-N- (N-cyclopentylcarbamoyl) amino] ethyl group, 2- [N- (N-cyclopentylcarbamoyl)-N-isobutylamino] ethyl group, 2-[N-cyclopentyl-N-(N-cyclopentylcarbamoyl)amino] ethyl group, 2- [N-cyclohexylmethyl-N- (N-cyclopentylcarbamoyl) amino] ethyl group, 2- [N- (N-cyclopentylcarbamoyl)-N-phenylamino] ethyl group, 2- [N-benzyl-N- (N-cyclopentylcarbamoyl) amino] ethyl group, 2- [N- (N-cyclohexylthiocarbamoyl)-N-methylamino] ethyl group, 2- [N-butyl-N- (N-cyclohexylthiocarbamoyl) amino] ethyl group, 2- [N- (N-cyclohexylthiocarbamoyl)-N-isobutylamino] ethyl group, 2- [N- (N-cyclohexylthiocarbamoyl)-N-cyclopentylamino] ethyl group, 2-[N-cyclohexylmethyl-N-(N-cyclohexylthiocarbamoyl) amino] ethyl group, 2- [N- (N-cyclohexylthiocarbamoyl)-N-phenylamino] ethyl group, 2- [N-benzyl-N- (N-cyclohexylthiocarbamoyl) amino] ethyl group, 2- (N-methyl-N-phenyloxycarbonylamino) ethyl group, 2- (N-butyl-N-phenyloxycarbonylamino) ethyl group, 2- (N-isobutyl-N-phenyloxycarbonylamino) ethyl group, 2-(N-cyclopentyl-N-phenyloxycarbonylamino)ethyl group, 2- (N-cyclohexylmethyl-N-phenyloxycarbonylamino) ethyl group, 2- (N-phenyl-N-phenyloxycarbonylamino) ethyl group, 2- (N-benzyl-N-phenyloxycarbonylamino) ethyl group, 2- [N-methyl-N- (N-phenylcarbamoyl) amino] ethyl group, 2- [N-butyl-N- (N-phenylcarbamoyl) amino] ethyl group, 2- [N-isobutyl-N- (N-phenylcarbamoyl) amino] ethyl group, 2- [N-cyclop entyl-N- (N-phenylcarbamoyl) amino] ethyl group, 2- [N-cyclohexylmethyl-N- (N-phenylcarbamoyl) amino] ethyl group, 2- [N-phenyl-N- (N-phenylcarbamoyl) amino] ethyl group, 2-[N-benzyl-N-(N-phenylcarbamoyl) amino] ethyl group, and the like.
When Rs in the formula (I) represents-N (Ry) (Rz), Rz is defined to have the same meaning as lAx, or Rz represents methyl group, ethyl group, or a-A5-Re group.
-A5-Re has the same meaning as defined above.
Particularly preferred examples of Rz include butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, l- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, 2-(N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxyearbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1-yl) carbonyl group, (morpholino-4-yl) carbonyl group, and the like.
Among the Rz, methyl group or ethyl group is particularly preferred when Ry is other than hydrogen atom.
Ry represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or a-A6-Qp group, or binds to Rz to form a saturated or unsaturated nitrogen-containing cyclic substituent having 3 to 7 atoms together with nitrogen atom to which they bind. The alkyl group having 1 to 8 carbon atoms is a linear or branched saturated alkyl group, a linear or branched partially unsaturated alkyl group, or an alkyl group which may contain a cyclic alkyl group having 3 to 7 carbon atoms. Examples include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, isopentyl group, 2-methylbutyl group, 2,2-dimethylpropyl group, hexyl group, 4-methylpentyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group, heptyl group, octyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, 3, 4-dimethylcyclopentyl group, 4-methylcyclohexyl group, 4, 4-dimethylcyclohexyl group, 4-ethylcyclohexyl group, 4-methylcyclohexylmethyl group, and the like.
-A6-Qp has the same meaning as defined above.
Particularly preferred examples of Ry include hydrogen atom, methyl group, ethyl group, isobutyl group, and the like.
Ry also binds to Rz to represents a saturated or unsaturated nitrogen-containing cyclic substituent having 3 to 7 atoms formed together with the nitrogen atom to which they bind. Specific examples thereof include cyclic substituents containing nitrogen atom such as 1-pyrrolidino group, 1-piperidino group, 1-homopiperidino group, 1'piperazino group, 4-morpholino group, pyrrol-1-yl group, imidazol-1-yl group, and pyrazol-1-yl group, and all of these are preferred.
The nitrogen-containing cyclic substituent may be substituted with one or two lower alkyl groups having 1 to 4 carbon atoms wherein the two alkyl groups may be the same or different. Examples of the lower alkyl having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, or t-butyl group.
Among the substituent-N (Ry) (Rz), particularly preferred examples include N, N-dimethylamino group, N-ethyl-N-methylamino group, N, N-diethylamino group, N-methyl-N-propylamino group, N-ethyl-N-propylamino group, N-isopropyl-N-methylamino group, N-ethyl-N-isopropylamino group, N-butylamino group, N-butyl-N-methylamino group, N-butyl-N-ethylamino group, N-isobutylamino group, N-isobutyl-N-methylamino group, N-ethyl-N-isobutylamino group, N- (2-ethylbutyl) amino group, N-(2-ethylbutyl)-N-methylamino group, N-cyclopentylamino group, N-cyclopentyl-N-methylamino group, N-cyclohexylamino group, N-cyclohexyl-N-methylamino group, N-cycloheptylamino group, N- (cyclopentylmethyl) amino group, N- (cyclopentylmethyl)-N-methylamino group, N- (cyclohexylmethyl) amino group, N- (cyclohexylmethyl)-N-methylamino group, N- (2-methylphenyl) amino group, N- (4-methylphenyl) amino group, N- (2-fluorophenyl) amino group, N- (3-fluorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (2-chlorophenyl) amino group, N' (3'chlorophenyl) amino group, N- (4-chlorophenyl) amino group, N- (indan-2-yl) amino group, N- (1-phenylethyl) amino group, N- [1- (2-fluorophenyl) ethyl] amino group, N- [1- (3-fluorophenyl) ethyl] amino group, N- [1- (4-fluorophenyl) ethyl] amino group, N- [1- (2-chlorophenyl) ethyfl amino group, N- [1- (3-chlorophenyl) ethyl] amino group, N- [1- (4-chlorophenyl) ethyl] amino group, N- (2-methylphenylmethyl) amino group, N-methyl-N- (2-methylphenylmethyl) amino group, N- (3-methylphenylmethyl) amino group, N-methyl-N- (3-methylphenylmethyl) amino group, N- (4-methylphenylmethyl) amino group, N-methyl-N- (4-methylphenylmethyl) amino group, N- (2-fluorophenylmethyl) amino group, N- (2-fluorophenylmethyl)-N-methylamino group, N- (3-fluorophenylmethyl) amino group, N- (3-fluorophenylmethyl) -N-methylamino group, N- (4-fluorophenylmethyl) amino group, N- (4-fluorophenylmethyl)-N-methylamino group, N- (2-chlorophenylmethyl) amino group, N- (2-chlorophenylmethyl)-N-methylamino group, N- (3-chlorophenylmethyl) amino group, N- (3-chlorophenylmethyl)-N-methylamino group, N- (4-chlorophenylmethyl) amino group, N- (4-chlorophenylmethyl)-N-methylamino group, N- (2, 3-difluorophenylmethyl) amino group, N- (2, 3-difluorophenylmethyl)-N-methylamino group, N-(2,4-difluorophenylmelthyl)amino group, N-(2, 4-difluorophenylmethyl)-N-methylamino group, N- (2, 5-difluorophenylmethyl) amino group, N- (2, 5-difluorophenylmethyl)-N-methylamino group, N- (3, 4-difluorophenylmethyl) amino group, N- (3, 4-difluorophenylmethyl)-N-methylamino group, N- (3, 5-difluorophenylmethyl) amino group, N- (3,5-difluorophenylmethyl)-N-methylamino group, N- (2, 3-dichlorophenylmethyl) amino group, N- (2, 3-dichlorophenylmethyl)-N-methylamino group, N- (2, 4-dichlorophenylmethyl) amino group, N- (2,4-dichlorophenylmethyl)-N-methylamino group, N- (2, 5-dichlorophenylmethyl) amino group, N- (2, 5-dichlorophenylmethyl)-N-methylamino group, N- (2, 6-dichlorophenylmethyl) amino group, N- (2, 6-dichlorophenylmethyl)-N-methylamino group, N- (3, 4-dichlorophenylmethyl) amino group, N- (3, 4-dichlorophenylmethyl) -N-methylamino group, N- (3,5-dichlorophenylmethyl) amino group, N- (3, 5-dichlorophenylmethyl)-N-methylamino group, N- [2- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [2- (trifluoromethyl) phenylmethyll amino group, N- [3- (trifluoromethyl) phenylmethyll amino group, N-methyl-N- [3- (trifluoromethyl) phenylmethyll amino group, N- [4- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [4- (trifluoromethyl) phenylmethyl] amino group, 1-pyrrolidino group, 1- (4-methylpiperidino) group, 1-homopiperidino group, and 4-morpholino group.
A most preferred example of Rs in the aforementioned general formula (I) include Rs which meets the conditions of : Rs is-D-Rx wherein D is a single bond and Rx represents Rb, and A1 and A2 in Rb are single bonds. Specific examples include phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2, 3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2, 3-difluorophenyl group, 2, 4-difluorophenyl group, 2, 5-difluorophenyl group, 3, 4-difluorophenyl group, 2, 3-dichlorophenyl group, 2,4-dichlorophenyl group, 2, 5-dichlorophenyl group, 2,6-dichlorophenyl group, 3, 4-dichlorophenyl group, 3, 5-dichlorophenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4- (N, N-dimethylamino) phenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, lH-indazol-5-yl group, or 1-methyl-lH-indazol-5-yl group.
AR in the formula (I) is defined to be a residue of a partially unsaturated or completely unsaturated condensed bicyclic carbon ring or heterocyclic ring (ar).
Further, AR may be substituted with one of Xa or two or more of the same or different Xa. The heterocyclic ring (ar) means a ring containing 1 to 4 the same or different ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom.
The"condensed bicyclic carbon ring or heterocyclic ring"means a partially unsaturated or completely unsaturated ring having 8 to 11 atoms. Preferred examples include a partially unsaturated or completely unsaturated ring consisting of 8 atoms formed by fusion of 5-membered heterocyclic rings containing 1 or 2 ring-constituting heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms, a partially unsaturated or completely unsaturated ring consisting of 9 atoms formed by fusion of a 5-membered heterocyclic ring containing 1 or 2 ring-constituting heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms and a 6-membered carbon ring or a 6-membered heterocyclic ring containing 1 or 2 ring-constituting heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms, and a partially unsaturated or completely unsaturated substituent consisting of 10 atoms formed by fusion of a 6-membered carbon ring or a 6-membered heterocyclic ring containing 1 or 2 ring-constituting heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms and a 6-membered carbon ring or 6-membered heterocyclic rings containing 1 or 2 ring-constituting heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atom. As the carbon ring constituting AR not containing a heteroatom, among the rings constituting AR, naphthalene ring is particularly preferred. Further, as the heterocyclic ring (ar) containing a heteroatom, among the rings constituting AR, those containing 1 or 2 ring-constituting heteroatoms are preferred.
As for AR in the formula (I), specific examples of preferred ring constituting AR include naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-1H-quinoline, benzo [d] isothiazole, 1H-indazole, benzo [c] isothiazole, 2H-indazole, imidazo l, 2-a] pyridine, 1H-pyrrolo [2, 3-b] pyridine, isoquinoline, dihydro-2H-isoquinoline, cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole, lH-pyrrolo [3, 2-b] pyridine, benzo [1, 2,5] thiadiazole, IH-benzotriazole, 1, 3-dihydropyrrolo [2, 3-b] pyridine, 1, 3-dihydrobenzimidazole, dihydro-3H-benzoxazole, phthalazine, [l, 8]naphthalidine, [1, 5] naphthalidine, 1H-pyrrolo [3, 2-c]pyridine, 1H-pyrrolo [2, 3-c] pyridine, 1H-pyrazolo [4, 3-b]pyridine, 1H-pyrazolo [4, 3-c] pyridine, IH-pyrazolo [3, 4-c pyridine, 1H-pyrazolo [3, 4-b] pyridine, [1, 2,4] triazolo [4, 3-a] pyridine, thieno [3, 2-c] pyridine, thieno [3, 2-b]pyridine, 1H-thieno[3,2-c]pyrazole, benzo[d]isoxazole, benzo[c]isoxazole, indolizine, 1,3-dihydroindol, lH-pyrazolo [3, 4-d] thiazole, 2H-isoindol, [1, 2,4] triazolo [1, 5-a] pyrimidine, lH-pyrazolo [3, 4-b] pyrazine, 1H-imidazo [4, 5-b] pyrazine, 7H-purine, 4H-chromene, and the like. Among them, naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-1H-quinoline, benzo [d] isothiazole, 1H-indazole, benzo [c] isothiazole, 2H-indazole, imidazo l, 2-a] pyridine, lH-pyrrolo [2, 3-b] pyridine, isoquinoline and dihydro-2H-isoquinoline constitute a particularly preferred group, and cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole, 1H-pyrrolo [3, 2-b] pyridine, benzo [1, 2,5] thiadiazole, 1H-benzotriazole, 1, 3-dihydropyrrolo [2, 3-b] pyridine, 1, 3-dihydrobenzimidazole and dihydro-3H-benzoxazole also constitute a particularly preferred group. Further, naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, quinoline, 1H-indazole and isoquinoline are particularly preferred.
AR binds to any of the ring-constituting carbon atoms C2, C3, C4, C5, and C6 in the aromatic ring (E) in the aforementioned formula (I) at an arbitrary carbon atom in AR. Preferred examples of the ring constituting AR include, as indicated with substitution position in the aromatic ring (E), naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, lH-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c]pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c]pyridin-5-yl group, lH-pyrrolo [2, 3-c] pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazaolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c]pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, lH-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b]pyridin-6-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4-yl group, benzo [d]isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo[d]isoxazo]-6-yl group, benzo [d]isoxazol-7-yl group, benzo [c]isoxazol-5-yl group, benzo [c]isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d]thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b]pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, 4H-chromen-5-yl group, and the like. Among them, naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, indol-5-yl group, indol-4-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, quinolin-6-yl group, quinolin-3-yl group, dihydro-lH-quinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, lH-indazol-4-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, dihydro-2H-isoquinolin-6-yl group, cinnolin-6-yl group, benzoxazol-5-yl group, and the like constitute a particularly preferred group, and naphthalen-2-yl group, benzofuran-5-yl group, benzo [b] thiophen-5-yl group, indol-5-yl group, benzothiazol-6-yl group, quinolin-6-yl group, quinolin-3-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, cinnolin-6-yl group, benzoxazol-5-yl group and the like are particularly preferred.
Further, AR may be substituted with one of Xa or the same or different two or more of Xa. Examples of substitution position of Xa include a carbon atom of AR not bonding to the aromatic ring (E), and/or when nitrogen atom is present, that nitrogen atom.
The substituent Xa represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, a saturated cyclic alkyl group having 3 to 7 carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, -(CH2) iRl4,-ORl°,-N (Rll) (Rl2),-SO2Rl3, or-COR27. However, when nitrogen atom is present in AR, Xa which may substitute on the nitrogen atom represents a linear or branched saturated alkyl group having 1 to 4 carbon atoms, a saturated cyclic alkyl group having 3 to 7 carbon atoms, or-(CH2) iRl4.
Preferred examples of the substituent Xa are oxo group, thioxo group, fluorine atom, chlorine atom, and trifluoromethyl group.
Examples of the linear or branched saturated alkyl group having 1 to 4 carbon atoms as the substituent Xa include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and among them, methyl group, ethyl group, and propyl group are particularly preferred.
Further, examples of the saturated cyclic alkyl group having 3 to 7 carbon atoms include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and the like.
- (CH2) iRl4 has the same meaning as defined above. Preferred examples are 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, and N, N-dimethylcarbamoylmethyl group, and a particularly preferred example is 2-hydroxyethyl group.
R10 in-ORl° represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or a-(CH2) iRl4 group, and among them, hydrogen atom is a particularly preferred example. Examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like. Among them, methyl group is particularly preferred.-(CH2) iRl4 has the same meaning as defined above.
Therefore, preferred examples of-ORl° are hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, and the like, and hydroxyl group, methoxy group, and 2-hydroxyethyloxy group are particularly preferred.
Rll in-N (R") (Rm) represents hydrogen atom, or a lower alkyl group having 1 to 4 carbon atoms, and R, 12 represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms,-COR15, or -SO2Rl6, or binds to Rll to form a 3-to 6-membered ring together with the nitrogen atom to which they bind to form a saturated nitrogen-containing cycloalkyl group or morpholino group. Rl5 in-COR15 represents a lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms, amino group, a mono-or dialkylamino group having 1 to 4 carbon atoms, or-A6-Qa. R16 in-S02Rl6 represents a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono- or dialkylamino group having 1 to 4 carbon atoms. Specific examples of-N (Rll) (Rl2) include amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, piperidino group, pyrrolidino group, morpholino group, 2-hydroxyethylamino group, formylamino group, acetylamino group, benzoyl group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, carbamoylamino group, N-methylcarbamoylamino group, N, N-dimethylcarbamoylamino group, methylsulfonylamino group, sulfamoylamino group, N-methylsulfamoylamino group, N, N-dimethylsulfamoylamino group, and the like. Among them, preferred examples are amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, and the like, and amino group, N-methylamino group, N, N-dimethylamino group, and 2-hydroxyethylamino group are particularly preferred.
R13 in-SO2Rl3 represents a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono-or dialkylamino group having 1 to 4 carbon atoms.
Preferred examples of-SO2Rl3 include methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, and the like.
R27 in-COR27 represents hydrogen atom, hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, a lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono-or dialkylamino group having 1 to 4 carbon atoms. Specific examples of-COR27 include formyl group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, acetyl group, propionyl group, carbamoyl group, N-methylcarbamoyl group, N, N-dimethylcarbamoyl group, and the like. Carboxyl group, acetyl group, carbamoyl group, N, N-dimethylcarbamoyl group, and the like are preferred examples, and carboxyl group is particularly preferred.
Preferred examples of the group Xa include oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N'dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, N, N-dimethylcarbamoyl group, and the like. Particularly preferred examples of the group Xa include oxo group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, amino group, N-methylamino group, N, N-dimethylamino group, 2-hydroxyethylamino group, carboxyl group, and the like. Preferred examples of the group Xa which may substitute on nitrogen atom include methyl group, ethyl group, propyl group, hydroxymethyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, and N, N-dimethylcarbamoylmethyl group. Among them, particularly preferred examples are methyl group, ethyl group, propyl group, and 2-hydroxyethyl group.
Preferred examples of AR substituted with the group Xa or unsubstituted AR include naphthalen-1-yl group, naphthalen-2-yl group, 6-fluoronaphthalen-2-yl group, 6-chloronaphthalen-2-yl group, 6- (trifluoromethyl) naphthalen-2-yl group, 5-hydroxynaphthalen-1-yl group, 5-hydroxynaphthalen-2-yl group, 6-hydroxynaphthalen-1-yl group, 6-hydroxynaphthalen-2-yl group, 7-hydroxynaphthalen-1-yl group, 7-hydroxynaphthalen-2-yl group, 5-methoxynaphthalen-1-yl group, 5-methoxynaphthalen-2-yl group, 6-methoxynaphthalen-1-yl group, 6-methoxynaphthalen-2-yl group, 7-methoxynaphthalen-1-yl group, 7-methoxynaphthalen-2-yl group, 5- (2-hydroxyethyloxy) naphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 7-(2-hydroxyethyloxy) naphthalen-2-yl group, 5- (carboxymethyloxy) naphthalen-2-yl group, 6- (carboxymethyloxy) naphthalen-2-yl group, 7- (carboxymethyloxy) naphthalen-2-yl group, 5- (N, N-dimethylcarbamoylmethyloxy) naphthalen-2-yl group, 6- (N, N-dimethylcarbamoylmethyloxy) naphthalen-2-yl group, 7- (N, N-dimethylcarbamoylmethyloxy) naphthalen-2-yl group, 5-aminonaphthalen-1-yl group, 5-aminonaphthalen-2-yl group, 6-aminonaphthalen-1-yl group, 6-aminonaphthalen-2-yl group, 7-aminonaphthalen-1-yl group, 7-aminonaphthalen-2-yl group, 5- (N-methylamino) naphthalen-1-yl group, 5- (N-methylamino) naphthalen-2-yl group, 6- (N-methylamino) naphthalen-1-yl group, 6- (N-methylamino) naphthalen-2-yl group, 7- (N-methylamino) naphthalen-1-yl group, 7- (N-methylamino) naphthalen-2-yl group, 5- (N, N-dimethylamino) naphthalen-1-yl group, 5- (N, N-dimethylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-l-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 7- (N, N-dimethylamino) naphthalen-1-yl group, 7-(N, N-dimethylamino) naphthalen-2-yl group, 5-(2-hydroxyethylamino) naphthalen-2-yl group, 6-(2-hydroxyethylamino)naphthalen-2-yl group, 7- (2-hydroxyethylamino) naphthalen-2-yl group, 5-acetylaminonaphthalen-2-yl group, 6-acetylaminonaphthalen-2-yl group, 6- (2-aminoacetylamino) naphthalen-2-yl group, 6- (2-hydroxyacetylamino) naphthalen-2-yl group, 7- (2-hydroxyacetylamino) naphthalen-2-yl group, 6-[(furan-2-carbonyl) amino] naphthalen-2-yl group, 7- [(furan-2-carbonyl) amino] naphthalen-2-yl group, 6- [ (benzene-2-carbonyl) amino] nap hthalen-2-yl group, 7- [ (benzene-2-carbonyl) amino] nap hthalen-2-yl group, 6-carbamoylaminonaphthalen-2-yl group, 6-methylsulfonylaminonaphthalen-2-yl group, 6-sulfamoylaminonaphthalen-2-yl group, 6- (N, N-dimethylsulfamoylamino) naphthalen-2-yl group, 6-methanesulfonylnaphthalen-2-yl group, 6-sulfamoylnaphthalen-2-yl group, 6- (N-methylsulfamoyl) naphthalen-2-yl group, 6- (N, N-dimethylsulfamoyl) naphthalen-2-yl group, 6-carboxynaphthalen-2-yl group, benzo [b] furan-4-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-4-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-4-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-4-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, 2-carboxybenzo [b] furan-4-yl group, 2-carboxybenzo [b] furan-5-yl group, 2-carboxy-3-methylbenzo [b] furan-4-yl group, 2-carboxy-3-methylbenzo [b] furan-5-yl group, 3-acetylbenzo [b] furan-4-yl group, 3-acetylbenzo [b] furan-5-yl group, 3-acetyl-2-methylbenzo [b] furan-4-yl group, 3-acetyl-2-methylbenzo [b]furan-5-yl group, 3-hydroxymethylbenzo [b]furan-4-yl group, 3-hydroxymethylbenzo [blfuran-5-yl group, 3-hydroxymethyl-2-methylbenzo [b]furan-4-yl group, 3-hydroxymethyl-2-methylbenzo [b] furan-5-yl group, benzolb] thiophen-4-yl group, benzo [b]thiophen-5-yl group, 2-methylbenzo [b]thiophen-4-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-4-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-4-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 2-carboxybenzo [b] thiophen-4-yl group, 2-carboxybenzo [b]thiophen-5-yl group, 2-carboxy-3-methylbenzo [b] thiophen-4-yl group, 2-carboxy-3-methylbenzo [b] thiophen-5-yl group, 3-acetylbenzo [b] thiophen-4-yl group, 3-acetylbenzo [b] thiophen-5-yl group, 3-acetyl-2-methylbenzo [b]thiophen-4-yl group, 3-acetyl-2-methylbenzo [b]thiophen-5-yl group, 3-hydroxymethylbenzo [b] thiophen-4-yl group, 3-hydroxymethylbenzo[b]thiophen-5-yl group, 3-hydroxymethyl-2-methylbenzo [b] thiophen-4-yl group, 3-hydroxymethyl-2-methylbenzo [b]thiophen-5-yl group, 1H-indol-4-yl group, 1H-indol-5-yl group, 2-methyl-1H-indol-4-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-4-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1H-indol-4-yl group, 2, 3-dimethyl-1H-indol-5-yl group, 2-carboxy-lH-indol-4-yl group, 2-carboxy-lH-indol-5-yl group, 2-carboxy-3-methyl-1H-indol-4-yl group, 2-carboxy-3-methyl-lH-indol-5-yl group, 3-acetyl-1H-indol-4-yl group, 3-acetyl-1H-indol-5-yl group, 3-acetyl-2-methyl-lH-indol-4-yl group, 3-acetyl-2-methyl-1H-indol-5-yl group, 3-hydroxymethyl-lH-indol-4-yl group, 3-hydroxymethyl-1H-indol-5-yl group, 3-hydroxymethyl-2-methyl-lH-indol-4-yl group, 3-hydroxymethyl-2-methyl-1H-indol-5-yl group, 1-methyl-1H-indol-4-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-lH-indol-4-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-1H-indol-4-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1,2, 3-trimethyl-1H-indol-4-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 2-carboxy-1-methyl-1H-indol-4-yl group, 2-carboxy-l-methyl-lH-indol-5-yl group, 2-carboxy-1, 3-dimethyl-lH-indol-4-yl group, 2-carboxy-1, 3-dimethyl-lH-indol-5-yl group, 3-acetyl-1-methyl-1H-indol-4-yl group, 3-acetyl-l-methyl-lH-indol-5-yl group, 3-acetyl-1, 2-dimethyl-lH-indol-4-yl group, 3-acetyl-1, 2-dimethyl-lH-indol-5-yl group, 3-hydroxymethyl-1-methyl-lH-indol-4-yl group, 3-hdyroxymethyl-1-methyl-1H-indol-5-yl group, 3-hydroxymethyl-1, 2-dimethyl-lH-indol-4-yl group, 3-hydroxymethyl-1, 2-dimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-4-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-4-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-4-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-4-yl group, l-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 2-carboxy-1-ethyl-1H-indol-4-yl group, 2-carboxy-1-ethyl-1H-indol-5-yl group, 2-carboxy-l-ethyl-3-methyl-lH-indol-4-yl group, 2-carboxy-1-ethyl-3-methyl-1H-indol-5-yl group, 3-acetyl-1-ethyl-1H-indol-4-yl group, 3-acetyl-1-ethyl-1H-indol-5-yl group, 3-acetyl-1-ethyl-2-methyl-1H-indol-4-yl group, 3-acetyl-1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-hydroxymethyl-lH-indol-4-yl group, l-ethyl-3-hydroxymethyl-lH-indol-5-yl group, 1-ethyl-3-hydroxymethyl-2-methyl-1H-indol-4-yl group, 1-ethyl-3-hydroxymethyl-2-methyl-1H-indol-5-yl group, 1-propyl-lH-indol-4-yl group, l-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-lH-indol-4-yl group, 2-methyl-1-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H-indol-4-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-4-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 2-carboxy-1-propyl-1H-indol-4-yl group, 2-carboxy-1-propyl-lH-indol-5-yl group, 2-carboxy-3-methyl-1-propyl-1H-indol-4-yl group, 2-carboxy-3-methyl-1-propyl-1H-indol-5-yl group, 3-acetyl-l-propyl-lH-indol-4-yl group, 3-acetyl-1-propyl-1H-indol-5-yl group, 3-acetyl-2-methyl-1-propyl-1H-indol-4-yl group, 3-acetyl-2-methyl-1-propyl-1H-indol-5-yl group, 3-hydroxymethyl-1-propyl-1H-indol-4-yl group, 3-hydroxymethyl-l-propyl-lH-indol-5-yl group, 3-hydroxymethyl-2-methyl-1-propyl-1H-indol-4-yl group, 3-hydroxymethyl-2-methyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH-indol-4-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-4-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-4-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H-indol-4-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, 2-carboxy-1- (2-hydroxyethyl)-lH-indol-4-yl group, 2-carboxy-1- (2-hydroxyethyl)-lH-indol-5-yl group, 2-carboxy-1-(2-hydroxyethyl)-3-methyl-1H-indol-4-yl group, 2-carboxy-1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group, 3-acetyl-1- (2-hydroxyethyl)-lH-indol-4-yl group, 3-acetyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, 3-acetyl-1- (2-hydroxyethyl)-2-methyl-lH-indol-4-yl group, 3-acetyl-1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-hydroxymethyl-lH-indol-4-yl group, 1- (2-hydroxyethyl)-3-hydroxymethyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-3-hydroxymethyl-2-methyl-lH-indol-4-yl group, 1- (2-hydroxyethyl)-3-hydroxymethyl-2-methyl-lH-indol-5-yl group, 1-carboxymethyl-1H-indol-4-yl group, 1-carboxymethyl-lH-indol-5-yl group, 1-carboxymethyl-2-methyl-lH-indol-4-yl group, 1-carboxymethyl-2-methyl-1H-indol-5-yl group, l-carboxymethyl-3-methyl-lH-indol-4-yl group, l-carboxymethyl-3-methyl-lH-indol-5-yl group, 1-carboxymethyl-2, 3-dimethyl-lH-indol-4-yl group, 1-carboxymethyl-2, 3-dimethyl-1H-indol-5-yl group, 2-carboxy-1-carboxymethyl-lH-indol-4-yl group, 2-carboxy-1-carboxymethyl-1H-indol-5-yl group, 2-carboxy-1-carboxymethyl-3-methyl-lH-indol-4-yl group, 2-carboxy-1-carboxymethyl-3-methyl-lH-indol-5-yl group, 3-acetyl-l-carboxymethyl-lH-indol-4-yl group, 3-acetyl-1-carboxymethyl-1H-indol-5-yl group, 3-acetyl-1-carboxymethyl-2-methyl-1H-indol-4-yl group, 3-acetyl-1-carboxymethyl-2-methyl-lH-indol-5-yl group, 1-carboxymethyl-3-hydroxymethyl-1H-indol-4-yl group, 1-carboxymethyl-3-hydroxymethyl-1H-indol-5-yl group, l-carboxymethyl-3-hydroxymethyl-2-methyl-lH-indol-4-yl group, 1-carboxymethyl-3-hydroxymethyl-2-methyl-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2- (N-methylamino) benzothiazol-6-yl group, 2- (N, N-dimethylamino) benzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, 2-methylquinolin-3-yl group, quinolin-6-yl group, 2-methylquinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 3-methylbenzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 3-methyl-lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1, 3-dimethyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-ethyl-3-methyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 3-methyl-1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indazol-5-yl group, 1-(carboxymethyl)-1H-indazol-5-yl group, 1-(carboxymethyl)-3-methyl-1H-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, benzo [c]isothiazol-5-yl group, 3-methylbenzo [c] isothiazol-5-yl group, 2-methyl-2H-indazol-5-yl group, 2, 3-dimethyl-2H-indazol-5-yl group, 2-ethyl-2H-indazol-5-yl group, 2-ethyl-3-methyl-2H-indazol-5-yl group, 2-propyl-2H-indazol-5-yl group, 3-methyl-2-propyl-2H-indazol-5-yl group, 2- (2-hydroxyethyl)-2H-indazol-5-yl group, 2- (2-hydroxyethyl) -3-methyl-2H-indazol-5-yl group, 2- (carboxymethyl) -2H-indazol-5-yl group, 2- (carboxymethyl)-3-methyl-2H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 2-methyl-imidazo [1, 2-a] pyridin-6-yl group, 3-methyl-imidazo [1, 2-a] pyridin-6-yl group, 2, 3-dimethyl-imidazo [l, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1, 2-dimethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dimethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 2, 3-dimethyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1, 2, 3-trimethyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b]pyridin-5-yl group, 1-ethyl-2-methyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-3-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-2, 3-dimethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 2-methyl-l-propyl-lH-pyrrolo [2, 3-b]pyridin-5-yl group, 3-methyl-1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 2, 3-dimethyl-1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (carboxymethyl) lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (carboxymethyl)-2-methyl-IH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (carboxymethyl)-3-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (carboxymethyl)-2, 3-dimethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-methylisoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, 2-methylquinazolin-6-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 2-methylquinoxalin-6-yl group, lH-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, l-methyl-lH-benzimidazol-5-yl group, 2-methyl-lH-benzimidazol-5-yl group, 1, 2-dimethyl-1H-benzimidazol-5-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 2-methylbenzoxazol-5-yl group, lH-pyrrolo [3, 2-b] pyridin-5-yl group, lH-pyrrolo [3, 2-b] pyridin-6-yl group, l-methyl-lH-pyrrolo [3, 2-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [3, 2-b]pyridin-5-yl group, 2-methyl-1H-pyrrolo [3, 2-b]pyridin-5-yl group, 3-methyl-1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1, 3-dimethyl-1H-pyrrolo [3, 2-b]pyridin-5-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzol, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1-methyl-lH-benzotriazol-5-yl group, 1-ethyl-1H-benzotriazol-5-yl group, 1, 3-dihydropyrrolo [2, 3-b]pyridin-2-on-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-2-on-4-yl group, 1-methyl-1, 3-dihydropyrrolo[2,3-b]pyridin-2-on-5-yl group, 1, 3-dihydrobenzimidazol-2-on-5-yl group, 1, 3-dihydrobenzimidazol-2-on-4-yl group, 1-methyl-1, 3-dihydrobenzimidazol-2-on-5-yl group, 1, 3-dihydrobenzimidazole-2-thion-5-yl group, 1, 3-dihydrobenzimidazole-2-thion-4-yl group, l'methyl'l, 3-dihydrobenzimidazole-2-thion-5-yl group, 3H-benzoxazol-2-on-6-yl group, 3H-benzoxazol-2-on-7-yl group, 3H-benzoxazol-2-on-5-yl group, 3H-benzoxazol-2-on-4-yl group, 3-methyl-3H-benzoxazol-2-on-6-yl group, 3H-benzoxazole-2-thion-6-yl group, 3H-benzoxazole-2-thion-7-yl group, 3H-benzoxazole-2-thion-5-yl group, 3H-benzoxazole-2-thion-4-yl group, 3-methyl-3H-benzoxazole-2-thion-6-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, 1-mnethyl-1H-pyrrolo [3, 2-c] pyridin-6-yl group, 1-ethyl-1H-pyrrolo [3, 2-c]pyridin-6-yl group, 2-methyl-1H-pyrrolo [3, 2-c] pyridin-6-yl group, 3-methyl-1H-pyrrolo [3, 2-c]pyridin-6-yl group, 1, 3-dimethyl-lH-pyrrolo [3, 2-c] pyridin-6-yl group, 1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1-methyl-1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-c] pyridin-5-yl group, 2-methyl-lH-pyrrolo [2, 3-c] pyridin-5-yl group, 3-methyl-1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1, 3-dimethyl-1H-pyrrolo] [2, 3-c] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, 1-methyl-1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrazolo [4, 3-b]pyridin-5-yl group, 3-methyl-lH-pyrazolo [4, 3-b] pyridin-5-yl group, 1, 3-dimethyl-lH-pyrazolo [4, 3-b]opyridin-5-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, 1-methyl-lH-pyrazolo [4, 3-c] pyridin-6-yl group, 1-ethyl-1H-pyrazolo [4, 3-c] pyridin-6-yl group, 3-methyl-1H-pyrazolo [4, 3-c]pyridin-6-yl group, 1, 3-dimethyl-lH-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, l-methyl-lH-pyrazolo [3, 4-c]pyridin-5-yl group, 1-ethyl-lH-pyrazolo [3, 4-c] pyridin-5-yl group, 3-methyl-lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1, 3-dimethyl-lH-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b]pyridin-4-yl group, 1-methyl-lH-pyrazolo [3, 4-b] pyridin-5-yl group, 1-ethyl-lH-pyrazolo [3, 4-b] pyridin-5-yl group, 3-methyl-lH-pyrazolo [3, 4-b]pyridin-5-yl group, 1, 3-dimethyl-1H-pyrazolo [3, 4-b] pyridin-5-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-7-yl group, 3-methyl [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c]pyridin-3-yl group, thieno [3, 2-c]pyridin-6-yl group, 2-methylthieno [3, 2-c] pyridin-2-yl group, 3-methylthieno [3, 2-c]pyridin-2-yl group, thieno [3, 2-b]pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3, 2-b]pyridin-6-yl group, 2-methylthieno [3, 2-blpyridin-2-yl group, 3-methylthieno [3, 2-b]pyridin-2-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c] pyrazol-4-yl group, 1-methyl-1H-thieno [3, 2-c] pyrazol-5-yl group, 1-ethyl-1H-thieno [3, 2-c] pyrazol-5-yl group, 3-methyl-1H-thieno [3, 2-c]pyrazol-5-yl group, 1, 3-dimethyl-1H-thieno [3, 2-c]pyrazol-5-yl group, benzo [d] isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [d]isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, 3-methylbenzo [d] isoxazol-5-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, 3-methylbenzo [c] isoxazol-5-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-2-on-5-yl group, 1, 3-dihydroindol-2-on-4-yl group, 1, 3-dihydroindol-2-on-6-yl group, 1-methyl-1, 3-dihydro-indol-2-on-5-yl group, lH-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, 2-methyl-2H-isoindol-5-yl group, 4H-chromen-6-yl group, 4H-chromen-5-yl group, chromen-4-on-7-yl group, chromen-4-on-6-yl group, and the like.
Particularly preferred examples include naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b]furan-5-yl group, 2, 3-dimethylbenzo [b]furan-5-yl group, benzo [b]thiophen-5-yl group, 2-methylbenzo [b]thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b]thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, l-ethyl-2-methyl-lH-indol-5-yl-group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, l-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, benzoxazol-5-yl group, and the like.
Particularly preferred examples include naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, benzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, benzoxazol-5-yl group, and the like.
In the formula (I), the group Y is defined to be hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms,- (CH2). N (RI8) (R'9), or-C (R20) 20C (O) A3R21, and among them, hydrogen atom is particularly preferred.
Examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like. Among them, methyl group, and ethyl group are particularly preferred.
Symbol m in-(CH2) mN (R18) (Rl9) is defined to be an integer of 2 or 3. R18 is the same as R19, or binds to R19 to represent a saturated nitrogen-containing cycloalkyl group forming a 3-to 6-membered ring together with nitrogen atom, or form morpholino group together with nitrogen atom, and R19 is defined to be methyl group, ethyl group, or propyl group. Examples of-(CH2) mN (R18) (Rl3) include 2- (N, N-dimethylamino) ethyl group, 2- (N, N-diethylamino) ethyl group, 2- (N, N-dipropylamino) ethyl group, 3- (N, N-dimethylamino) propyl group, 3- (N, N-diethylamino) propyl group, 2- (N, N-dipropylamino) propyl group, 2-pyrrolidin-1-ylethyl group, 2-piperidin-1-ylethyl group, 2-morpholin-4-ylethyl group, 3-pyrrolidin-1-ylpropyl group, 3-piperidin-1-ylpropyl group, 3-morpholin-4-ylpropyl group, and the like.
R20 in-C (R20) 20C (O) A3R21 is defined to be hydrogen atom, methyl group, ethyl group, or propyl group. R21 is defined to be a lower alkyl group having 1 to 4 carbon atoms, a cyclic saturated alkyl group having 3 to 6 carbon atoms group, or phenyl group. Examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like, and examples of the cyclic saturated alkyl group having 3 to 6 carbon atoms group include cyclopropyl group, cyclobutyl group, cyclopentyl group, and cyclohexyl group. A3 is defined to be a single bond, or oxygen atom. Examples of-C (R20) 2OC (O) A3R2l include acetoxymethyl group, propionyloxymethyl group, butyryloxymethyl group, (2-methylpropionyl) oxymethyl group, (2, 2-dimethylpropionyl) oxymethyl group, cyclopropionyloxymethyl group, cyclopentanoyloxymethyl group, cyclohexanoyloxymethyl group, phenylcarboxymethyl group, 1-acetoxy-1-methylethyl group, 1-methyl-1-(2-methylpropionyloxy) ethyl group, 1-cyclopentanoyloxy-l-methylethyl group, 1-cyclohexanoyloxy-1-methylethyl group, methoxycarbonyloxymethyl group, ethoxycarbonyloxymethyl group, isopropyloxycarbonyloxymethyl group, t-butyloxycarbonyloxymethyl group, cyclopropyloxycarbonyloxymethyl group, cyclopentyloxycarbonyloxymethyl group, cyclohexyloxycarbonyloxymethyl group, phenyloxycarbonyloxymethyl group, 1-methoxycarbonyloxy-1-methylethyl group, 1-ethoxycarbonyloxy-1-methylethyl group, 1-isopropyloxycarbonyloxy-1-methylethyl group, 1-t-butyloxycarbonyloxy-1-methylethyl group, 1-cyclopropyloxycarbonyloxy-1-methylethyl group, 1-cyclopentyloxyearbonyloxy-1-methylethyl group, 1-cyclohexyloxycarbonyloxy-1-methylethyl group, 1-methyl-1-phenyloxycarbonyloxyethyl group, and the like.
In a preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CHz) n-, symbol n represents an integer of 1 to 3.
AR binds to C2, Rs binds to any of the atoms C3, C4 and C5, and a ring-constituting carbon atom to which Rs does not bind among C3, C4, and C5 may be replaced with V.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents-D-Rx, or-N (Ry) (Rz). D represents oxygen atom, or sulfur atom. Rx represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom,-N (methyl)-, or -N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, A1 represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene. A5 represents -C (O)-,-C (S)-, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4'methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N-(furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N-(thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxyearbonylamino group.
Rz represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2-(4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N'cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with nitrogen atom.
AR represents naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b]pyridin-5-yl group, 1, 3-dihydroppyrrolo[2,3-b]pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c]pyridin-45-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-clpyridin-4-yl group, 1H-pyrazolo [3, 4-c]pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, lH-pyrazolo [3, 4-b] pyridin-5-yl group, lH-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b]pyridinb-6-yl group, 1H-thieno [3, 2-c]pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, lH-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (these groups may be substituted with one of Xa or two or more of the same or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another preferred embodiment of the present invention, the compound represented by the formula (1) or a salt thereof satisfies all of the following requirements.
Link represents-(CH2) n-, symbol n represents an integer of 1 to 3.
AR binds to C3, Rs binds to any of the atoms C4, C5, and C6, and a ring-constituting carbon atom to which Rs does not bind among C4, C5, and C6 may be replaced with V.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents-D-Rx, or-N (Ry) (Rz). D represents oxygen atom, or sulfur atom. Rx represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb, or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom,-N (methyl)-, or -N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, A1 represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene. A5 represents -C (O)-,-C (S)-, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N-(pyridin-2-yl) amino group, N-(pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N-(thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group. Rz represents a group as any of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4'chlorophenyl) ethyl group, 2-[2-(trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4'methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N-(4-chlorophenyl)thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-l-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogen atom to which they binds.
AR represents naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, lH-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, lH-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, lH-pyrrolo [3, 2-c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, lH-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c]pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b]pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b]pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b] pyridin-6-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In a preferred embodiment of the present invention, a compound or a salt thereof satisfying all of the following requirements is excluded from the compound represented by the formula (I) or a salt thereof.
Link represents- (CH2) n-, symbol n represents an integer of 1 to 3.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 represents a ring-constituting carbon atom which may be substituted with Zx, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
Zx represents fluorine atom, chlorine atom, nitro group, amino group, methyl group, or a OR9 group, and R9 represents hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
Rs represents-O-Rx. Rx represents a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or represents Ra or Rb, Q in Rb represents a residue of a partially unsaturated or completely unsaturated monocyclic or condensed bicyclic carbon ring or heterocyclic ring (q), and binds to A2 at an arbitrary position on the ring. The heterocyclic ring (q) contains one or two of the same or different ring-constituting heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom.
AR represents a residue of naphthalene, benzofuran, benzo [b] thiophene, indole, benzothiazole, dihydro-3H-benzothiazole, quinoline, dihydro-lH-quinoline, benzo [d] isothiazole, IH-indazole, benzo [c] isothiazole, 2H-indazole, imidazo [1, 2-a] pyridine, lH-pyrrolo [2, 3-b] pyridine, isoquinoline, or dihydro-2H-isoquinoline (the aforementioned residue may be substituted with one of Xa or two or more of the same or different Xa).
In another preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents-(CH2) n-, symbol n represents an integer of 1 to 3.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with V, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents'O'Rx. Rx represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom, -N (methyl)-, or-N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom, -N (methyl) -, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, Al represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene.
A5 represents-C (O)-,-C (S)-, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4'methylphenyl) amino group, N- (4-chlorophenyl) amino group, N' (4-fluorophenyl) amino group, N-(pyridin-2-yl) amino group, N-(pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N-(thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group.
AR represents any one of cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, lH-pyrrolo [3, 2-b] pyridin-5-yl group, lH-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, lH-pyrrolo [3, 2-c]pyridin-4-yl group, lH-pyrrolo [2, 3-c]pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c]pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, lH-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b]pyridin-2-yl group, thieno [3, 2-b]pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b]pyridin-6-yl group, 1H-thieno [3, 2-c]pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo[d]isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c]isoxazol-5-yl group, benzo [c]isoxazol-4-yl group, benzo [c]isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, lH-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, and 4H-chromen-5-yl group (these groups may be substituted with one of Xa or two or more of the same or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- H2) n-symbol n represents an integer of 1 to 3.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents-S-Rx. Rx represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom, - N (methyl), or-N (ethyl) - (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, Al represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene.
A5 represents-C (O)-,-C (S) -, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N-(thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group.
AR represents naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7'yl group, dihydro-lH-quinolin-6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, 1H-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b]pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H-benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [l, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, lH-pyrrolo [3, 2-c] pyridin-6-yl group, l H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, l H-pyrazolo [4, 3-b] pyridin-5-yl group, III-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-c]pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b]pyridin-6-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a]pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b]pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (these groups may be substituted with one of Xa or two or more of the same or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethoxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 1 to 3.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, and C2, C5 and C6 represent unsubstituted ring-constituting carbon atom.
Rs represents-N (Ry) (Rz). Rz represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2-[3-(trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2-(phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl. group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N'cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-l-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogen atom to which they bind.
AR represents naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro'lH'quinolin'6'yl group, dihydro-lH-quinolin-5-yl group, benzo [dlisothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d]isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, lH-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c]isothiazol-5-yl group, benzo [c]isothiazol-4-yl group, benzo [c]isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, l H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-yl group, l H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b]pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, lH-pyrrolo [3, 2-c]pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c]pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b]pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c]pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3, 2-b] pyridin-6-yl group, lH-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c] pyrazol-4-yl group, benzo [d]isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [d]isoxazol-6-yl group, benzo [d]isoxazol-7-yl group, benzo [c]isoxoazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c]isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, lH-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (these groups may be substituted with one of Xa or two or more of the same or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 1 to 3.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with V, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents-D-Rc, and D represents oxygen atom or sulfur atom. Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene.
A5 represents-C (O)-,-C (S)-, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4'methylphenyl) amino group, N' (4-chlorophenyl) amino group, N' (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group.
AR represents naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-1H-quinolin-6-yl group, dihydro-1H-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, lH-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7~yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, lH-pyrrolo [3, 2-b]pyridin-5-yl group, lH-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzol, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihdyropyrrolo[2,3-b]pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [l, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, lH-pyrrolo [3, 2-c]pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, lH-pyrazolo [4, 3-b] pyridin-6-yl group, 1H-pyrazolo [4, 3-c] pyridin-6-yl group, 1H-pyrazolo [4, 3-c]pyridiin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-clpyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b]pyrridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [d]isoxazol-6-yl group, benzo [d]isoxazol-7-yl group, benzo [c]isoxazol-5-yl group, benzo [c]isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo[1,5-a]pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (these groups may be substituted with one of Xa or two or more of the same or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link is- (CH2) n-, n is an integer of 1 to 3, C3 is carbon atom bound with AR, C4 is carbon atom bound with Rs, C5 may be replaced with V, C2 and C6 are unsubstituted ring-constituting carbon atoms, V is nitrogen atom or V is carbon atom substituted with Zx, Zx is any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group, Rs is-D-Rx, D is a single bond, Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rx is Rb or Rc (provided that Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, or dihydrobenzodioxyl group), A2 is a single bond, oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)- or - N (ethyl) -, A1 represents ethylene), R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group, p in Rc is an integer of 2 or 3, A4 is a single bond or methylene, A5 is-C (O)-,-C (S) -, or -S (0) 2-, Rd is hydrogen atom, or methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylamino group, AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [blthiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, 1H-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c] isothiazol-4-yl group, benzo [c]isothiazol-6-yl group, benzo [c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, lH-pyrrolo [2, 3-b]pyriodin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, lH-benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, lH-pyrazolo [4, 3-b] pyridin-5-yl group, 1H-pyrazolo [4, 3-b]pyridin-6-yl group, lH-pyrazolo [4, 3-c]pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b]pyridin-5-yl group, thieno [3, 2-b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, 1H-thieno [3, 2-c]pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d]isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d]thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a]pyrimidin-6-yl group, 1H-pyrazolo [3, 4-b]pyrazin-5-yl group, 1H-imidazo [4, 5-b]pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of the same or different Xa), Xa is oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, or N, N-dimethylcarbamoyl group, and Y is hydrogen atom, methyl group, or ethyl group.
In a particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C2 represents carbon atom to which AR bonds, C3 represents carbon atom to which Rs bonds, C4 may be replaced with V, and C5 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group.
Rs represents-O-Rx. Rx represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2-(2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2-(4-chlorophenyl) ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group, 2- [3- (trifluoromethyl) phenyl ethyl group, 2- [4- (trifluoromethyl) phenyll ethyl group, 2- [4- (N, N- dimethylamino) phenyll ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6-(2-hydoryxethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo[b]furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, l-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-porpyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a3pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, l'oxo'l, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents -(CH2) n, symbol n represents an integer of 2.
C2 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with V, and C3 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group.
Rs represents-O-Rx. Rx represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1-(2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2-(4-methoxyphenyl)ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyll ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2-(N-phenyl-N-methylamino) ethyl group, and 2-(N-ethyl-N-phenylamino) ethyl group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1H-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, l-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, l-ethyl-3-methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, l-ethyl-3-hydroxy-lH-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-IH-pyrrolo [2, 3-b]pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C5 represents carbon atom to which Rs bonds, and C2, C4 and C6 represent unsubstituted ring-constituting carbon atom.
Rs represents'O'Rx. Rx represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyll ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2-(phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6-(2-hydorxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzolb] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-1H-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, l-propyl-lH-indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, l-propyl-lH-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroyx-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H-pyrrolo [2, 3-b]pyridin-5-yl group, isoquinolin-6-yl group, l-oxorl, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 represents nitrogen atom, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
Rs represents-O-Rx. Rx represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, l- (2-fluorophenyl) ethyl group, l- (3-fluorophenyl) ethyl group, l- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4-(trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2-(phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6-(2-hydoryxethylamino)naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo[b]furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzolb] thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-lH-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-IH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C6 represents carbon atom substituted with Zx, and C2 and C5 represent unsubstituted ring-constituting carbon atom.
Zx represents fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group.
Rs represents'O'Rx. Rx represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2Eyl group, 4, 7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, l' (3'chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3-(trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2-(4-fouorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4-(trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo[b]furan-5-yl group, 3-methylbenzo lb] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d]isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazoll, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b]pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b]pyridin-5-yl group, 1-(2-hydroxyethyl)-1H-pyrrolo [2, 3-b]pyrridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, and C2, C5 and C6 represent unsubstituted ring-constituting carbon atom.
Rs represents-N (Ry) (Rz). Rz represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5'dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4'fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, or morpholino group together with nitrogen atom to which they bonds.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [blfuran-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, l-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, l'oxo'l, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, and C2, C5 and C6 represent unsubstituted ring-constituting carbon atom.
Rs represents-N (Ry) (Rz). -N (Ry) (Rz) is any one of N, N-dimethylamino group, N-ethyl-N-methylamino group, N, N-diethylamino group, N-methyl-N-propylamino group, N-ethyl-N-propylamino group, N-isopropyl-N-methylamino group, N-ethyl-N-isopropylamino group, N-butylamino group, N-butyl-N-methylamino group, N-butyl-N-ethylamino group, N-isobutylamino group, N-isobutyl-N-methylamino group, N-ethyl-N-isobutylamino group, N- (2-ethylbutyl) amino group, N- (2-ethylbutyl)-N-methylamino group, N-cyclopentylamino group, N-cyclopentyl-N-methylamino group, N-cyclohexylamino group, N-cyclohexyl-N-methylamino group, N-cycloheptylamino group, N' (cyclopentylmethyl) amino group, N- (cyclopentylmethyl)-N-methylamino group, N- (cyclohexylmethyl) amino group, N-(cyclohexylmethyl)-N-methylamino group, N- (2-methylphenyl) amino group, N- (4-methylphenyl) amino group, N- (2-fluorophenyl) amino group, N- (3-fluorophenyl) amino group, N- 4-fluorophenyl) amino group, N- (2-chlorophenyl) amino group, N- (3-chlorophenyl) amino group, N- (4-chlorophenyl) amino group, N-(indan-2-yl) amino group, N- (1-phenylethyl) amino group, N- [1- (2-fluorophenyl) ethyl] amino group, N- [1- (3-fluorophenyl) ethyl] amino group, N- [1- (4-fluorophenyl) ethyl] amino group, N- [1- (2-chlorophenyl) ethyl] amino group, N- [1- (3-chlorophenyl) ethyl] amino group, N- [1- (4-chlorophenyl) ethyl] amino group, N- (2-methylphenylmethyl) amino group, N-methyl-N- (2-methylphenylmethyl) amino group, N- (3-methylphenylmethyl) amino group, N-methyl-N- (3-methylphenylmethyl) amino group, N- (4-methylphenylmethyl) amino group, N-methyl-N- (4-methylphenylmethyl) amino group, N- (2-fluorophenylmethyl) amino group, N- (2-fluorophenylmethyl)-N-methylamino group, N- (3-fluorophenylmethyl) amino'group, N- (3-fluorophenylmethyl)-N-methylamino group, N- (4-fluorophenylmethyl) amino group, N- (4-fluorophenylmethyl)-N-methylamino group, N- (2-chlorophenylmethyl) amino group, N- (2-chlorophenylmethyl)-N-methylamino group, N- (3-chlorophenylmethyl) amino group, N- (3-chlorophenylmethyl)-N-methylamino group, N- (4-chlorophenylmethyl) amino group, N- (4-chlorophenylmethyl)-N-methylamino group, N- (2, henylmethyl) amino group, N- (2, 3-difluorophenylmethyl)-N-methylamino group, N- (2, 4-difluorophenylmethyl) amino group, N- (2, 4-difluorophenylmethyl)-N-methylamino group, N- (2, 5-difluorophenylmethyl) amino group, N- (2,5-difluorophenylmethyl)-N-methylamino group, N- (3, 4-difluorophenylmethyl) amino group, N- (3, 4-difluorophenylmethyl)-N-methylamino group, N- (3, 5-difluorophenylmethyl) amino group, N- (3, 5-difluorophenylmethyl)-N-methylamino group, N- (2, 3-dichlorophenylmethyl) amino group, N- (2, 3-dichlorophenylmethyl)-N-methylamino group, N- (2, 4-dichlorophenylmethyl) amino group, N- (2,4-dichlorophenylmethyl)-N-methylamino group, N- (2, 5-dichlorophenylmethyl) amino group, N- (2, 5-dichlorophenylmethyl)-N-methylamino group, N- (2, 6-dichlorophenylmethyl) amino group, N- (2, 6-dichlorophenylmethyl)-N-methylamino group, N- (3, 4-dichlorophenylmethyl) amino group, N- (3, 4-dichlorophenylmethyl)-N-methylamino group, N- (3, 5-dichlorophenylmethyl) amino group, N- (3,5-dichlorophenylmethyl)-N-methylamino group, N- [2- (trifluoromethyl) phenylmethyl] amino group, N-methyl-N- [2- (trifluoromethyl) phenylmethyll amino group, N- [3- (trifluoromethyl) p henylmethyl] amino group, N-methyl-N- [3- (trifluoromethyl) phenylmethyll amino group, N- [4- (trifluoromethyl) p henylmethyl] amino group, N-methyl-N- [4- (trifluoromethyl) phenylmethyl] amino group, 1'pyrrolidino group, 1- (4-methylpiperidino) group, 1-homopiperidino group, or 4-morpholino group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzolb] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3'dimethyl'l' (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b]pyrridin-5-yl group, 1-propyl-lH-pyrrolol2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 represents carbon atom substituted with Zx, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
Zx represents N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents'O'Rx. Rx represents a group as any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2-(2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1H-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-IH-indol-5-yl group, 2, 3'dimethyl'l' (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [dlisothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with V, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, and Zx represents a group as any one of chlorine atom, bromine atom, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group.
Rs represents-O-Rc. p in Rc represents an integer of 2, and A4 represents a single bond or methylene. A5 represents-C (O)-,-C (S)-, or-S (O) 2-. Rd represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, and 4-fluorophenylmethyl group. Re represents a group as any one of isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4'methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, pyrrolidino group, piperidino group, and morpholino group.
AR represents a group as any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b]thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1H-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-IH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2-, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group.
The group Y represents hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents -(CH2)n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with V, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, Zx is any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group, Rs represents-D-Rx and D represents a single bond. Rx is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2,3-difluorophenyl group, 2, 4-difluorophenyl group, 2, 5-difluorophenyl group, 3,4-difluorophenyl group, 2, 3-dichlorophenyl group, 2, 4-dichlorophenyl group, 2, 5-dichlorophenyl group, 2, 6-dichlorophenyl group, 3, 4-dichlorophenyl group, 3, 5-dichlorophenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4- (N, N-dimethylamino) phenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1H-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, biphenyl-2-yl group, biphenyl 3-yl group, biphenyl-4-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2-(2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, or 2- (N-ethyl-N-phenylamino) ethyl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo[b]furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b]thiophen-5-yl group, 3-methylbenzo [b]thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, l-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, l-ethyl-lH-indazol-5-yl group, 1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, l-ethyl-3-hydroxy-lH-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2,3-b] pyridin-5-yl group, l-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, C5 may be replaced with V, and C2 and C6 represent unsubstituted ring-constituting carbon atom.
V represents nitrogen atom, or carbon atom substituted with Zx, Zx is any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, or N, N-dimethylamino group, Rs represents-D-Rx and D represents a single bond. Rx is phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2, 3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2,3-difluorophenyl group, 2,4-difluorophenyl group, 2,5-difluorophenyl group, 3, 4-difluorophenyl group, 2, 3-dichlorophenyl group, 2, 4-dichlorophenyl group, 2, 5-dichlorophenyl group, 2, 6-dichlorophenyl group, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4- (N, N-dimethylamino) phenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1H-indazol-5-yl group, or 1-methyl-1H-indazol-5-yl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6-(N-methylamino) naphthalen-2-yl group, 6-(N,N-dimethylamino)naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [blfuran-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo[b]thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1 (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
In another particularly preferred embodiment of the present invention, the compound represented by the formula (I) or a salt thereof satisfies all of the following requirements.
Link represents- (CH2) n-, symbol n represents an integer of 2.
C3 represents carbon atom to which AR bonds, C4 represents carbon atom to which Rs bonds, and C2, C5, and C6 represent unsubstituted ring-constituting carbon atom.
Rs represents-D-Rx and D represents a single bond. Rx is phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2, 3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2, 3-difluorophenyl group, 2,4-difluorophenyl group, 2,5-difluorophenyl group, 3,4-difluorophenyl group, 2, 3-dichlorophenyl group, 2, 4-dichlorophenyl group, 2, 5-dichlorophenyl group, 2, 6-dichlorophenyl group, 3, 4-dichlorophenyl group, 3, 5-dichlorophenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 4-(N, N-dimethylamino) phenyl group, indan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group, lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, lH-indazol-5-yl group, or 1-methyl-lH-indazol-5-yl group, AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6-(2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a]pyridin-6-yl group, 1H-pyrrolo [2,3-b]pyridin-5-yl group, l-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, or benzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethyl group.
Compound (I) of the present invention may have one or more asymmetric carbons depending on types of substituents. For example, as for a compound wherein the group Rs contains one or more asymmetric carbons, two kinds of optical isomers exist when the number of asymmetric carbon is 1, and when the number of asymmetric carbons is 2, four kinds of optical isomers and two kinds of diastereomers exist. Pure stereoisomers including optical isomers and diastereoisomers, any mixtures thereof, racemates and the like of the stereoisomers fall within the scope of the present invention. Further, Compound (I) of the present invention may exist as geometrical isomers based on a cycloalkyl ring structure, and any geometrical isomers in pure forms, and any mixtures of the geometrical isomers also fall within the scope of the present invention. Mixtures such as racemates may sometimes be preferred from a viewpoint of easiness for manufacture.
As a salt of Compound (I) of the present invention, a pharmaceutically acceptable salt is preferred. It is meant that, when at least one of the conditions (1) to (3) is satisfied: (1) Y is hydrogen atom ; (2) the group AR contains carboxyl group or phenolic hydroxyl group ; (3) the group Zx is phenolic hydroxyl group, and the like, then the compound forms 1 to 3 alkali salts depending on the number of acidic groups. Examples the alkali salts include, for example, salts with inorganic bases such as sodium and ammonia and salts with organic bases such as triethylamine.
Alternatively, it is meant that, when at least one of the conditions (1) to (4) is satisfied : (1) the group Rs has properties as a base as in a compound wherein Rs contains a substituted or unsubstituted amino group and the like ; (2) AR itself is a cyclic substituent having properties as a base ; (3) the group Ar contains a substituted or unsubstituted amino group ; (4) any carbon atom in the aromatic ring (E) is replaced with V, and V is nitrogen atom, V is carbon atom substituted with Zx, and Zx is a substituted or unsubstituted amino group and the like, then the compound forms 1 to 4 acidic salts depending on the number of basic groups.
Examples of the acidic salts include, for example, salts with inorganic acids such as hydrochloric acid and sulfuric acid and salts with organic acids such as acetic acid and citric acid.
C2', C3', C4', C5', and C6'in the aromatic ring (E') in the aforementioned formula (II) each represent a ring-constituting carbon atom. Among them, any ring-constituting carbon atom to which Rs'and G do not bind may be replaced with V. The substitution positions of Rs', G, and V are similar to those described in the explanations of the substitution positions of Rs (corresponding to the position of Rs'), AR (corresponding to the position of the group G), and V (corresponding to the position of V') in the aforementioned formula (I).
V'represents nitrogen atom, or represents carbon atom substituted with Zx'.
Zx'has the same meaning as that of Zx, provided that when Zx contains hydroxyl group (OH), the hydroxyl group may be protected with Rpl, and when Zx contains amino group (NH), the amino group may be protected with Rp2.
Rs'represents-D-Rx'or-N (Ry') (Rz'). -D-Rx'and-N (Ry') (Rz') have the same meanings as those of-D-Rx and-N (Ry) (Rz) mentioned above, respectively.
Provided that when-D-Rx and-N (Ry) (Rz) contain hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx and-N (Ry) (Rz) contains amino group (NH), the amino group may be protected with Rp2.
Rpl represents, for example, a silyl group substituted with 3 of identical or different linear or branched saturated alkyl groups having 1 to 4 carbon atoms or phenyl groups, tetrahydropyranyl group, tetrahydrofuryl group, allyl group, propargyl group, benzyl group which may be substituted with one Tl or two or more identical or different T1,-CH2-U-Rp3,-C (O) Rp3, -C (O) ORp3, or the like. U represents oxygen atom, or sulfur atom, and Rp3 represents hydrogen atom, a linear or branched saturated alkyl group having 1 to 4 carbon atoms, trimethylsilylethyl group, chloromethyl group, trichloromethyl group, trifluoromethyl group, 9-fluorenylmethyl group, adamantyl group, allyl group,-A6-Qp, or the like. Rp2 represents, for example, benzyl group which may be substituted with one of T1 or two or more of identical or different T,-C (O) Rp3, -C (O) ORp3, or the like. However, the protective groups of hydroxyl group and amino group are not limited to these, and they can be chosen by referring and examining methods for introduction of protective groups and deprotection described in usual publications in the chemical field, for example, Protective Groups In Organic Synthesis, THIRD EDITION, published by John Wiley & Sons or the references cited therein.
G represents chlorine atom, bromine atom, iodine atom, mesylate group, triflate group, or an arenesulfonate group of which aromatic moiety may be substituted with one of T1 or two or more identical or different Tl. Examples of the arenesulfonate group include, for example, benzenesulfonate group, p-toluenesulfonate group, mesitylenesulfonate group, 2,4, 6-triisopropylbenzenesulfonate group, 4-fluorobenzenesulfonate group, 2, 5-dichlorobenzenesulfonate group, 3- (trifluoromethyl) benzenesulfonate group, pentafluorobenzenesulfonate group, 2-nitrobenzenesulfonate group, 2, 4-dinitrobenzenesulfonate group, and the like. Preferred examples of G include chlorine atom, bromine atom, iodine atom, triflate group, and the like, and bromine atom and iodine atom are particularly preferred examples.
Y'represents a lower alkyl group having 1 to 4 carbon atoms. Examples of the lower alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, and the like. Among these, methyl group, and ethyl group are particularly preferred examples.
In the aforementioned formula (II), n and D have the same meaning as defined above.
In a preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 1 to 3.
The group G binds to C2', Rs'binds to any of the atoms C3', C4'and C5', and a ring-constituting carbon atom to which Rs'does not bind among C3', C4', and C5'may be substituted with V'.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx' contains amino group, the amino group may be protected with Rp2.
Rs'represents-D-Rx'or-N (Ry') (Rz'). D represents oxygen atom or sulfur atom. Rx'represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom,-N (methyl)-, or -N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, Al represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, A1 represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene. A5 represents -C (O)-,-C (S) -, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N-(pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N-(thiophen-2-yl) amino group, N-(thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxyearbonylamino group. Rz'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyllethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group,- N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-l-yl) carbonyl group, (piperidino-1-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry' represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogen atom to which they bonds. Provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group (OH), the hydroxyl group may be protected with Rpl, and when-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2.
The group G represents chlorine atom, bromine atom, iodine atom, or triflate group.
The group Y'represents methyl group, or ethyl group.
In another preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 1 to 3.
The group G binds to C3', Rs'binds to any of the atoms C4', C5', and C6', and a ring-constituting carbon atom to which Rs'does not bind among C4', C5'and C6'may be replaced with V'.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx' contains amino group, the amino group may be protected with Rp2.
Rs'represents-D-Rx', or-N (Ry') (Rz'). D represents oxygen atom or sulfur atom. Rx'represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom,-N (methyl)-, or -N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, A1 represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene. A5 represents -C (O)-,-C (S) -, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- 4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group. Rz'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2-(phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2-(N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylearbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-l-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry' represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with nitrogen atom. Provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2.
The group G represents chlorine atom, bromine atom, iodine atom, or triflate group.
The group Y'represents methyl group, or ethyl group.
In a particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C2'represents carbon atom to which the group G bonds, C3'represents carbon atom to which Rs'binds, C4'may be replaced with V', and C5'and C6'represent an unsubstituted ring-constituting carbon atom.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2 Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2' (4'fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyll ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C2'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C5'may be replaced with V', and C3'and C6'represent an unsubstituted ring-constituting carbon atom.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx' contains hydroxyl group, the hydroxyl group may be protected with Rp 1, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2-[2-(trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2-14-(trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C5'represents carbon atom to which Rs'binds, and C2', C4'and C6'represent an unsubstituted ring-constituting carbon atom.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, l-phenylethyl group, l- (2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C5'represents nitrogen atom, and C2'and C6' represent an unsubstituted ring-constituting carbon atom.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2-[2-(trifluoromethyl) phenyl] ethyl group, 2-13- (trifluoromethyl) phenyl] ethyl group, 2- [4-(trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C6'represents carbon atom substituted with Zx', and C2'and C5'represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C5'represents carbon atom substituted with Zx', or unsubstituted carbon atom, and C2'and C6'represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-S-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3-(trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2-[2-(trifluoromethyl) phenyllethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyll ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C5'represents carbon atom substituted with Zx', or unsubstituted ring-constituting carbon atom, and C2'and C6'represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-N (Ry') (Rz'). Rz'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1-(2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) p henyll ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t'butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyelohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxyearbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxyearbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry' represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, or morpholino group together with the nitrogen atom to which they bonds. Provided that when-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when Ry'or Rz' contains amino group, the amino group may be protected with Rp2.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C5'represents carbon atom substituted with Zx', and C2'and C6'represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group. Provided that when the substituted Zx'contains amino group (NH), the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1-(3-fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1-(3-chlorophenyl) ethyl group, l- (4'chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N N-dimethylamino) p henyll ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
In another particularly preferred embodiment, the compound represented by the formula (II) satisfies all of the following requirements.
Symbol n represents an integer of 2.
C3'represents carbon atom to which the group G bonds, C4'represents carbon atom to which Rs'binds, C5'represents carbon atom substituted with Zx', or unsubstituted carbon atom, and C2'and C6'represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'have the same meaning as that of Rc, provided that when Rc contains hydroxyl group (OH), the hydroxyl group may be protected with Rpl. p in Rc represents an integer of 2, and A4 represents a single bond or methylene. A5 represents-C (O)-,-C (S) -, or-S (0) 2-. Rd represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, and 4-fluorophenylmethyl group. Re represents a group as any one of isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, pyrrolidino group, piperidino group, and morpholino group.
The group G represents bromine atom, or iodine atom.
The group Y'represents methyl group, or ethyl group.
C2', C3', C4', C5', and C6'in the aromatic ring (E') in the aforementioned formula (III) each represent a ring-constituting carbon atom. Any ring-constituting carbon atom to which Rs'and AR'do not bond among them may be replaced with V'.
The substitution positions of Rs', AR', and V'are similar to those described in the explanations of the substitution positions of Rs (corresponding to the position of Rs'), AR (corresponding to the position of the group AR'), and V (corresponding to the position of V') in the aforementioned formula (I).
AR'has the same meaning as that of AR mentioned above, provided that when AR contains hydroxyl group, the hydroxyl group may be protected with Rpl.
In this case, the hydroxyl group includes OH in carboxyl group (COOH). When the substituted AR contains amino group, the amino group represents a substituent, which may be protected with Rp2. Examples of the amino group, which may be protected include NH present in a ring constituting AR, for example, as in indole ring, indazole ring, and the like.
Rs', V', n, and D in the aforementioned formula (III) have the same meanings as those defined above. Rpl, and Rp2 also have the same meanings as those defined above.
In a preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
AR'binds to C2', Rs'binds to any of the atoms C3', C4', and C5', and a ring-constituting carbon atom to which Rs'does not bind among C3', C4', and C5'may be replaced with V.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx' contains amino group, the amino group may be protected with Rp2.
Rs'represents-D-Rx'or-N (Ry') (Rz'). D represents oxygen atom or sulfur atom. Rx'represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom,-N (methyl)-, or -N (ethyl)- (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, Al represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene. A5 represents -C (O)-,-C (S)-, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N- (thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group. Rz'represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4-(trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2-(2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2- (N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4'fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylearbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N'cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-l-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry' represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogen atom to which they bond. However,-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or - N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2.
AR'represents any one of naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-1H-quinolin-6-yl group, dihydro-lH-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, 1H-indazol-5-yl group, lH-indazol-4-yl group, lH-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c]isothiazol-4-yl group, benzo [c]isothiazol-6-yl group, benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1H-pyrrolo [2, 3-b] pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, lH-benzimidazol-5-yl group, lH-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, 1H-pyrrolo [3, 2-b] pyridin-5-yl group, 1H-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H-benzotriazol-5-yl group, lH-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b]pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, lH-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c]pyridin-5-yl group, lH-pyrrolo [2, 3-c] pyridin-4-yl group, lH-pyrazolo [4, 3-b]pyridin-5-yl group, lH-pyrazolo [4, 3-b]pyridin-6-yl group, lH-pyrazolo [4, 3-c]pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, 1H-pyrazolo [3, 4-c] pyridin-5-yl group, 1H-pyrazolo [3, 4-c] pyridin-4-yl group, lH-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-6-yl group, [1, 2,4] triazolo [4, 3-a]pyridin-7-yl group, thieno [3, 2-c] pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3,2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b] pyridin-6-yl group, 1H-thieno [3, 2-c] pyrazol-5-yl group, lH-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d] thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b] pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, and 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of identical or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
AR'binds to C3', Rs'binds to any of the ring-constituting carbon atoms C4', C5', and C6', and a ring-constituting carbon atom to which Rs'does not bind among C4', C5', and C6'may be replaced with V'.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group, methoxy group, amino group, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx' contains amino group, the amino group may be protected with Rp2.
Rs'represents-D-Rx'or-N (Ry') (Rz'). D represents oxygen atom or sulfur atom. Rx'represents butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rb represents a group as any one of phenyl group, thienyl group, furyl group, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group, indolyl group, and dihydrobenzodioxyl group. A2 represents a single bond, oxygen atom, sulfur atom, -N (methyl) -, or - N (ethyl) - (provided that when A2 represents oxygen atom, sulfur atom,-N (methyl)-, or-N (ethyl)-, A1 represents ethylene). R2 and R3 independently represent hydrogen atom, methyl group, fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, dimethylamino group, acetylamino group, or methylsulfonylamino group (provided that when Q represents phenyl group, A1 represents a single bond, or unsubstituted methylene, and A2 represents a single bond, one of R2 and R3 represents a substituent other than hydrogen atom). Symbol p in Rc represents an integer of 2 or 3, and A4 represents a single bond or methylene. A5 represents -C (O)-,-C (S) -, or-S (0) 2-. Rd represents hydrogen atom, or a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Re represents any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group, amino group, N-methylamino group, N, N-dimethylamino group, N-ethylamino group, N, N-diethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N' (4-methylphenyl) amino group, N- (4-chlorophenyl) amino group, N- (4-fluorophenyl) amino group, N- (pyridin-2-yl) amino group, N- (pyridin-3-yl) amino group, N- (pyridin-4-yl) amino group, N- (furan-2-yl) amino group, N- (furan-3-yl) amino group, N- (thiophen-2-yl) amino group, N-(thiophen-3-yl) amino group, pyrrolidino group, piperidino group, morpholino group, methyloxycarbonylamino group, and ethyloxycarbonylamino group. Rz'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3'chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, 2-(N-ethyl-N-phenylamino) ethyl group, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group, cyclopropylthiocarbonyl group, cyclopentylcarbonyl group, cyclopentylthiocarbonyl group, cyclohexylcarbonyl group, cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group, phenylsulfonyl group, 4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group, N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoyl group, isobutyloxycarbonyl group, N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group, N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group, N'phenylcarbamoyl group, N-phenylthiocarbamoyl group, 4-methylphenyloxycarbonyl group, N- (4-methylphenyl) carbamoyl group, N- (4-methylphenyl) thiocarbamoyl group, 4-chlorophenyloxycarbonyl group, N- (4-chlorophenyl) carbamoyl group, N- (4-chlorophenyl) thiocarbamoyl group, 4-fluorophenyloxycarbonyl group, N- (4-fluorophenyl) carbamoyl group, N- (4-fluorophenyl) thiocarbamoyl group, (pyrrolidino-1-yl) carbonyl group, (piperidino-1-yl) carbonyl group, and (morpholino-4-yl) carbonyl group. Ry' represents hydrogen atom, methyl group, ethyl group, or isobutyl group, or binds to Rz'to form pyrrolidino group, piperidino group, piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, or pyrazol-1-yl group together with nitrogen atom. Provided that when-D-Rx'or-N (Ry') (Rz') contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when-D-Rx'or-N (Ry') (Rz') contains amino group, the amino group may be protected with Rp2.
AR'represents any one of naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group, benzo [b] thiophen-5-yl group, benzo [b] thiophen-4-yl group, benzo [b] thiophen-2-yl group, indol-5-yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-yl group, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group, quinolin-7-yl group, dihydro-lH-quinolin-6-yl group, dihydro-1H-quinolin-5-yl group, benzo [d] isothiazol-5-yl group, benzo [d] isothiazol-4-yl group, benzo [d] isothiazol-6-yl group, benzo [d] isothiazol-7-yl group, lH-indazol-5-yl group, lH-indazol-4-yl group, 1H-indazol-6-yl group, benzo [c] isothiazol-5-yl group, benzo [c]isothiazol-4-yl group, benzo [c] isothiazol-6-yl group, benzo [c] isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-yl group, 2H-indazol-6-yl group, imidazo [1, 2-a] pyridin-6-yl group, imidazo [1, 2-a] pyridin-7-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, lH-pyrrolo [2, 3-b]pyridin-4-yl group, isoquinolin-6-yl group, isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group, dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group, cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group, lH-pyrrolo [3, 2-b] pyridin-5-yl group, lH-pyrrolo [3, 2-b] pyridin-6-yl group, benzo [1, 2,5] thiadiazol-5-yl group, benzo [1, 2,5] thiadiazol-4-yl group, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-5-yl group, 1, 3-dihydropyrrolo [2, 3-b] pyridin-4-yl group, 1, 3-dihydrobenzimidazol-5-yl group, 1, 3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group, phthalazin-5-yl group, [1, 8] naphthalidin-3-yl group, [1, 8] naphthalidin-4-yl group, [1, 5] naphthalidin-3-yl group, [1, 5] naphthalidin-4-yl group, 1H-pyrrolo [3, 2-c] pyridin-6-yl group, 1H-pyrrolo [3, 2-c] pyridin-4-yl group, 1H-pyrrolo [2, 3-c] pyridin-5-yl group, 1H-pyrrolo [2, 3-c] pyridin-4-yl group, 1H-pyrazolo [4, 3-b] pyridin-5-yl group, lH-pyrazolo [4, 3-b] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-6-yl group, lH-pyrazolo [4, 3-c] pyridin-4-yl group, lH-pyrazolo [3, 4-c] pyridin-5-yl group, lH-pyrazolo [3, 4-c] pyridin-4-yl group, lH-pyrazolo [3, 4-b] pyridin-5-yl group, 1H-pyrazolo [3, 4-b] pyridin-4-yl group, [1, 2,4] triazolo [4, 3-a] pyridin-6-yl group, [1, 2, 4] triazolo [4, 3-a]pyridin-7-yl group, thieno [3, 2-c]pyridin-2-yl group, thieno [3, 2-c] pyridin-3-yl group, thieno [3, 2-c] pyridin-6-yl group, thieno [3, 2-b] pyridin-2-yl group, thieno [3, 2-b] pyridin-3-yl group, thieno [3, 2-b] pyridin-5-yl group, thieno [3, 2-b] pyridin-6-yl group, lH-thieno [3, 2-c]pyrazol-5-yl group, 1H-thieno [3, 2-c] pyrazol-4-yl group, benzo [d] isoxazol-5-yl group, benzo [d] isoxazol-4-yl group, benzo [d] isoxazol-6-yl group, benzo [d] isoxazol-7-yl group, benzo [c] isoxazol-5-yl group, benzo [c] isoxazol-4-yl group, benzo [c] isoxazol-6-yl group, benzo [c] isoxazol-7-yl group, indolizin-7-yl group, indolizin-6-yl group, indolizine-8-yl group, 1, 3-dihydroindol-5-yl group, 1, 3-dihydroindol-4-yl group, 1, 3-dihydroindol-6-yl group, 1H-pyrazolo [3, 4-d]thiazol-5-yl group, 2H-isoindol-5-yl group, 2H-isoindol-4-yl group, [1, 2,4] triazolo [1, 5-a] pyrimidin-6-yl group, lH-pyrazolo [3, 4-b]pyrazin-5-yl group, 1H-imidazo [4, 5-b] pyrazin-5-yl group, 7H-purin-2-yl group, 4H-chromen-6-yl group, and 4H-chromen-5-yl group (the aforementioned groups may be substituted with one of Xa or two or more of identical or different Xa). The substituent Xa represents a group as any one of oxo group, thioxo group, fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, N, N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxy group, N, N-dimethylcarbamoylmethyloxy group, amino group, methylamino group, dimethylamino group, 2-hydroxyethylamino group, carbamoylamino group, acetylamino group, furan-2-carboxyamino group, 2-hydroxyacetylamino group, 2-aminoacetylamino group, methylsulfonylamino group, (N, N-dimethylsulfamoyl) amino group, methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group, N, N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoyl group, and N, N-dimethylcarbamoyl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In a particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
C2'represents carbon atom to which AR'binds, C3'represents carbon atom to which Rs'binds, C4'may be replaced with V', and C5'and C6'represent an unsubstituted ring-constituting carbon atom.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, l- (3'fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2-(3-fluorophenyl) ethyl group, 2' (4'fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyll ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyll ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2-(N-ethyl-N-phenylamino) ethyl group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b]thiophen-5-yl group, 2-methylbenzo [blthiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1-(2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-1H-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, einnolin-6-yl group, and benzoxazol-5-yl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
C2'represents carbon atom to which AR'binds, C4'represents carbon atom to which Rs'binds, C5'may be replaced with V', and C3'and C6'represent an unsubstituted ring-constituting carbon atom.
V'represents nitrogen atom, or carbon atom substituted with Zx', and Zx' represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group. Provided that when Zx' contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5, 6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, l' (2'fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1-(4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3, 5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4-(trifluoromethyl)phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyllethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo[b]furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, l-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo l, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rp l, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
C3'represents carbon atom to which AR'binds, C5'represents carbon atom to which Rs'binds, and C2', C4'and C6'represent an unsubstituted ring-constituting carbon atom.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, l- (4'chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2-(N-ethyl-N-phenylamino) ethyl group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, 1-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, l-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, l-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-lH-indazol-5-yl group, imidazoll, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yt group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
C3'represents carbon atom to which AR'binds, C4'represents carbon atom to which Rs'binds, C5'represents nitrogen atom, and C2'and C6'represent an unsubstituted ring-constituting carbon atom.
Rs' represents -O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4, 7-dimethoxyindan-2-yl group, 5, 6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1-(2-chlorophenyl) ethyl group, l' (3'chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2, 4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2-[2-(trifluoromethyl)phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo[b]furan-5-yl group, 2, 3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, 1H-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-1H-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, l-ethyl-2-methyl-1H-indol-5-yl group, l-ethyl-3-methyl-lH-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-1-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1-(2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-lH-indazol-5-yl group, 1-ethyl-lH-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1- (2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, l'oxo'l, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
C3'represents carbon atom to which AR'binds, C4'represents carbon atom to which Rs'binds, C6'represents carbon atom substituted with Zx', and C2'and C5' represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4, 7-difluoroindan-2-yl group, 5, 6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1'phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, l' (4'fluorophenyl) ethyl group, 1- (2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2, 3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2, 3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3, 6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2-(2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4-(trifluoromethyl)phenyl]ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2-(phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzoMthiophen-5-yl group, 2-methylbenzo [bjthiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-lH-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-lH-indol-5-yl group, l-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, l-propyl-lH-indol-5-yl group, 2-methyl-l-propyl-lH-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-1H-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b]pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-propyl-1H-pyrrolo [2, 3-b]pyridin-5-yl group, 1-(2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, l'oxo'l, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements..
C3'represents carbon atom to which AR'binds, C4'represents carbon atom to which Rs'binds, C5'represents carbon atom substituted with Zx', and C2'and C6' represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N, N-dimethylamino group, N, N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, and N, N-dimethylsulfamoylamino group. Provided that when the substituted Zx'contains amino group (NH), the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'represents any one of butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4, 7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4, 7-dichloroindan-2-yl group, 5, 6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1- (2-fluorophenyl) ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (4-fluorophenyl) ethyl group, 1-(2-chlorophenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (4-chlorophenyl) ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2, 3-dimethylphenylmethyl group, 3, 5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2, 5-difluorophenylmethyl group, 3, 4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2, 4-dichlorophenylmethyl group, 2, 5-dichlorophenylmethyl group, 2, 6-dichlorophenylmethyl group, 3, 4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2- (trifluoromethyl) phenylmethyl group, 3- (trifluoromethyl) phenylmethyl group, 4- (trifluoromethyl) phenylmethyl group, 2- (2-methylphenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2-(4-methylphenyl) ethyl group, 2- (2-methoxyphenyl) ethyl group, 2- (3-methoxyphenyl) ethyl group, 2- (4-methoxyphenyl) ethyl group, 2- (2-fluorophenyl) ethyl group, 2- (3-fluorophenyl) ethyl group, 2- (4-fluorophenyl) ethyl group, 2- (2-chlorophenyl) ethyl group, 2- (3-chlorophenyl) ethyl group, 2- (4-chlorophenyl) ethyl group, 2- [2- (trifluoromethyl) phenyl] ethyl group, 2- [3- (trifluoromethyl) phenyl] ethyl group, 2- [4- (trifluoromethyl) phenyl] ethyl group, 2- [4- (N, N-dimethylamino) phenyl] ethyl group, 2-phenyloxyethyl group, 2- (2-chlorophenyloxy) ethyl group, 2- (3-chlorophenyloxy) ethyl group, 2- (4-chlorophenyloxy) ethyl group, 2- (phenylthio) ethyl group, 2- (N-phenyl-N-methylamino) ethyl group, and 2- (N-ethyl-N-phenylamino) ethyl group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2, 3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-1h-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1, 2, 3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-1H-indol-5-yl group, 1-propyl-lH-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-l-propyl-lH-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1-(2-hydroxyethyl)-1H-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2, 3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, 1H-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-yl group, 3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1-ethyl-1H-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolol2, 3-b] pyridin-5-yl group, 1-(2-hydroxyethyl)-1H-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
In another particularly preferred embodiment, the compound represented by the formula (III) satisfies all of the following requirements.
C3'represents carbon atom to which AR'binds, C4'represents carbon atom to which Rs'binds, C5'represents carbon atom substituted with Zx', or an unsubstituted ring-constituting carbon atom, and C2'and C6'represent an unsubstituted ring-constituting carbon atom.
Zx'represents any one of fluorine atom, methyl group, hydroxyl group, amino group, N-methylamino group, and N, N-dimethylamino group, provided that when Zx'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when the substituted Zx'contains amino group, the amino group may be protected with Rp2.
Rs'represents-O-Rx'. Rx'have the same meaning as that of Re, provided that when Rc contains hydroxyl group, the hydroxyl group may be protected with Rpl. p in Rc represents an integer of 2, and A4 represents a single bond or methylene. A5 represents-C (O)-,-C (S)-, or-S (0) 2-. Rd represents a group as any one of methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group, and 4-fluorophenylmethyl group. Re represents a group as any one of isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl'group, phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxy group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group, N- (4-methylphenyl) amino group, N' (4'chlorophenyl) amino group, N- (4-fluorophenyl) amino group, pyrrolidino group, piperidino group, and morpholino group.
AR'represents any one of naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group, 6- (2-hydroxyethyloxy) naphthalen-2-yl group, 6-aminonaphthalen-2-yl group, 6- (N-methylamino) naphthalen-2-yl group, 6- (N, N-dimethylamino) naphthalen-2-yl group, 6- (2-hydroxyethylamino) naphthalen-2-yl group, benzo [b] furan-5-yl group, 2-methylbenzo [b] furan-5-yl group, 3-methylbenzo [b] furan-5-yl group, 2,3-dimethylbenzo [b] furan-5-yl group, benzo [b] thiophen-5-yl group, 2-methylbenzo [b] thiophen-5-yl group, 3-methylbenzo [b] thiophen-5-yl group, 2,3-dimethylbenzo [b] thiophen-5-yl group, lH-indol-5-yl group, 2-methyl-lH-indol-5-yl group, 3-methyl-1H-indol-5-yl group, 2, 3-dimethyl-lH-indol-5-yl group, 1-methyl-lH-indol-5-yl group, 1, 2-dimethyl-1H-indol-5-yl group, 1, 3-dimethyl-lH-indol-5-yl group, 1,2, 3-trimethyl-lH-indol-5-yl group, 1-ethyl-1H-indol-5-yl group, l-ethyl-2-methyl-lH-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-yl group, 1-ethyl-2, 3-dimethyl-lH-indol-5-yl group, 1-propyl-1H-indol-5-yl group, 2-methyl-1-propyl-1H-indol-5-yl group, 3-methyl-1-propyl-1H-indol-5-yl group, 2, 3-dimethyl-l-propyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-lH-indol-5-yl group, 1- (2-hydroxyethyl)-2-methyl-lH-indol-5-yl group, 1- (2-hydroxyethyl)-3-methyl-lH-indol-5-yl group, 2, 3-dimethyl-1- (2-hydroxyethyl)-lH-indol-5-yl group, benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group, 2-oxo-2,3-dihydrobenzothiazol-6-yl group, 2-oxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-2, 3-dihydrobenzothiazol-6-yl group, 2-thioxo-3-methyl-2, 3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group, quinolin-6-yl group, 2-oxo-1, 2-dihydroquinolin-6-yl group, benzo [d] isothiazol-5-yl group, lH-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group, l-ethyl-1H-indazol-5-yl group, 1-propyl-lH-indazol-5-yl group, 1-(2-hydroxyethyl)-lH-indazol-5-yl group, 3-hydroxy-lH-indazol-5-yl group, 3-hydroxy-l-methyl-lH-indazol-5-yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo [1, 2-a] pyridin-6-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group, 1-methyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-ethyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, l-propyl-lH-pyrrolo [2, 3-b] pyridin-5-yl group, 1- (2-hydroxyethyl)-lH-pyrrolo [2, 3-b] pyridin-5-yl group, isoquinolin-6-yl group, 1-oxo-1, 2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, and benzoxazol-5-yl group. Provided that when AR'contains hydroxyl group, the hydroxyl group may be protected with Rpl, and when substituted AR'contains amino group, the amino group may be protected with Rp2.
Compound (I) of the present invention can be produced by, for example, employing the reactions according to the following various methods.
[Preparation Method 1] (Step a-1) As shown in the following scheme 1 : (Schemel) a compound of the present invention represented by the formula (Ia') wherein Y represents a lower alkyl group having 1 to 4 carbon atoms, and Rs, AR, and V on or in the aromatic ring (E) may be protected [hereinafter simply referred to as "Compound (Ia')"], which falls within the scope of Compound (I) of the present invention, can be prepared by reacting a compound represented by the formula (II) [simply referred to as"Compound (II)"hereinafter] with a boronic acid derivative represented by the formula (IV) [hereinafter simply referred to as"Compound (IV)"]. n, C2'to C6', Rs', AR', Y'and G in the formulas have the same meanings as defined above. In the formula of Compound (IV), Ll and L2 independently represent hydroxyl group, an alkoxyl group having 1 to 8 carbon atoms (e. g. , methoxy group, ethoxy group, propoxy group, isopropoxy group, cyclohexyloxy group), or a substituted or unsubstituted phenyloxy group, or Ll and L2 bind to each other to represent a 5-or 6-membered cyclic ester of an arylboric acid (e. g., 9- borabicyclo [3,3, l] nonane, 1,3, 2-dioxaborolane, 4,4, 5, 5-tetramethyl-1, 3, 2- dioxaborolane), which forms a ring containing boron atom [this ring may be saturated or unsaturated, may be a ring containing a heteroatom other than boron (e. g. , oxygen atom), and may be further substituted].
Further, as shown in the following scheme 2: Rs'C5'=C6, '1-a-1 C X (CH2)"-COOY' 3<_ AR' (Ia) Rs'c5 C"2) AR'-G /3'-Cz' Ll_ B c-I-C I (V) (VI) 12 L2 (Scheme2) an example of the method for preparing Compound (Ia') includes a method of reacting a combination of a compound represented by the formula (V) [hereinafter simply referred to as"Compound (V)"] and a compound represented by the formula (VI) [hereinafter simply referred to as"Compound (VI)"].
Examples include a method of preparing Compound (Ia') by performing the Suzuki reaction described in, for example, Jikken Kagaku Koza, 4th Edition (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 25, p. 403 with a combination mentioned either in the scheme l or scheme 2 or the both. A specific example includes a reaction of Compound (II) [or Compound (V)] with Compound (IV) [or Compound (VI)] in a solvent in the presence of a commercially available palladium catalyst or a catalyst prepared from a palladium complex and a ligand, and a base.
As the palladium catalyst, a commercially available catalyst such as tetrakis (triphenylphosphine) palladium, tetrakis (methyldiphenylphosphine) palladium, dichlorobis (triphenylphosphine) palladium, dichlorobis (tri-o- tolylphosphine) palladium, dichlorobis (tricyclohexylphosphine) palladium, dichlorobis (triethylphosphine) palladium, palladium acetate, palladium chloride, bis (acetonitrile) palladium chloride, tris (dibenzylideneacetone) dipalladium and bis (diphenylphosphinoferrocene) palladium chloride may be purchased and added to the reaction system, per se, or a catalyst may be added which is separately prepared from palladium acetate, tris (dibenzylideneacetone) dipalladium or the like and arbitrary ligands and isolated. Further, a catalyst considered to actually participate in the reaction may also be prepared by mixing palladium acetate, tris (dibenzylideneacetone) dipalladium or the like and arbitrary ligands in the reaction system. The valence of palladium may be 0 or may be +2. Examples of the ligand include phosphine ligands such as trifurylphosphine, tri (o- tolyl) phosphine, tri (cyclohexyl) phosphine, tri (t-butyl) phosphine, dicyclohexylphenylphosphine, 1, 1'-bis (di-t-butylphosphino) ferrocen, 2- dicyclohexylphosphino-2'-dimethylamino-1, 1'-biphenyl and 2- (di-t- butylphosphino) biphenyl and phosphine mimic ligands such as imidazol-2- ylidenecarbenes. Chemical equivalents of the palladium catalyst may be one equivalent or a catalytic amount, and the amount may preferably be 0.01 to 20.0 mol %, and most preferably be 0.10 to 10.0 mol %.
Examples of the base include sodium carbonate, potassium carbonate, cesium carbonate, cesium fluoride, potassium fluoride, potassium phosphate, potassium acetate, triethylamine, potassium hydroxide, sodium hydroxide, sodium methoxide, lithium methoxide and the like. The reaction temperature is, for example, preferably 20°C to 150°C, and particularly preferable examples include 20°C to 120°C.
The reaction system may be either a two-phase system of water and an organic solvent, or a homogeneous system of a water-containing organic solvent or an organic solvent. As for the organic solvent, examples include uses of hydrocarbon-type solvents such as toluene, xylene and hexane, halogen-type solvents such as methylene chloride, sulfoxide-type solvents such as dimethyl sulfoxide, amide-type solvents such as dimethylformamide, ether-type solvents such as tetrahydrofuran, dioxane and diglyme, alcohol-type solvents such as methanol and ethanol, nitrile-type solvents such as acetonitrile, ketone-type solvents such as acetone and cyclohexanone, ester-type solvents such as ethyl acetate, heterocyclic- type solvents such as pyridine and the like. Two or more kinds of organic solvents may be mixed and used.
For the reaction conditions, Miyaura, N. , Suzuki, A. , Chemical Review, 1995, vol. 95, p. 2457 ; Snieckus, V., Chemical Review, 1990, vol. 90, p. 879 and the like and references cited therein can be referred to.
When hydroxyl group or amino group reactive under the aforementioned reaction conditions or inhibiting the reactions exists in the group AR', Rs'or V'in the aromatic ring (E'), this substituent is preferably protected.
When a protective group of hydroxyl group or amino group exist in the group AR', Rs'or V in the aromatic ring (E') of the compound (Ia') prepared as described above, such a protective group can be eliminated during or after the preparation of Compound (Ia') to convert the compound into Compound (I) of the present invention. As for selection, introduction and deprotection of these protective groups of hydroxyl group and amino group, ordinary chemical publications, for example, Protective Groups In Organic Synthesis THIRD EDITION, John Wiley & Sons) and references cited therein can be referred to.
[Preparation Method 1] (Step a-2) As Compound (IV), a compound commercially available as a reagent may be used, or as shown in the following scheme 3: L1 1-a-2 <BR> <BR> <BR> <BR> <BR> AR'-B < AR'-G <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> (vol) (IV) (Scheme3) the compound can be produced from Compound (VI), which is commercially available or can be synthesized by a known method or a similar method thereto, according to the method described in the aforementioned reference (Chemical Review, vol. 95, p. 2457,1995) or the method described in Satoh, Y. et al., SYNTHESIS, p. 1146,1994 or according to the references cited therein.
For example, examples include a method of preparing Compound (VI) by converting Compound (VI) into a lithio-compound using an alkyl lithium such as n- butyl lithium and t-butyl lithium, then reacting the product with a trialkyl borate and treating the product with a mineral acid such as hydrochloric acid, sulfuric acid, and phosphoric acid and a method of to preparing Compound (VI) by performing a cross-coupling reaction of Compound (VI) and an (alkoxyl) diboron in the presence of a palladium catalyst and a base.
An example of the preparation method of Compound (V) includes a method of subjecting Compound (II) to a reaction similar to that of the aforementioned Step a-2, as shown in the following scheme 4 : Rs'c5=cs, C4\\/ (E) -- n-COOY- /C3 B C5,-r61 1-a-2 C 3l-c2l mu (Scheme4) [Preparation Method 1] (Step b) As shown in the following scheme 5 : Rs'C51 C f I), - Hai l-b Rs-= C6 1* C3'C2 (VII) (Scheme5) a compound represented by the formula (IIh) (hereinafter simply referred to as "Compound (IIh)"), which correspond to the compounds (II) wherein G represents a halogen atom such as chlorine atom, bromine atom or iodine atom, can be prepared by halogenating a compound represented by the formula (VII) [this compound is simply referred to as"Compound (VII)"], which is commercially available or can be prepared by a known method or a method similar thereto. In the formula of Compound (IIh), the group Hal represents a halogen atom, which may be any of chlorine atom, bromine atom and iodine atom. As for the halogenation, examples of chlorination include a preparation method described in ordinary publications in the filed of chemistry, for example, Shin Jikken Kagaku Koza (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 14, p. 354. Examples of the method include a method utilizing chlorine (Cl2), a method utilizing sulfuryl chloride, and the like. Examples of bromination include a preparation method described in ordinary publications in the filed of chemistry, for example, Shin Jikken Kagaku Koza (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 14, p. 354. Examples of the method include a method utilizing bromine (Br2), a method utilizing N-bromosuccinimide, and the like. Examples of iodination include a preparation method described in ordinary publications in the filed of chemistry, for example, Shin Jikken Kagaku Koza (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 14, p. 423. Examples of the method include a method utilizing iodine (I2), a method utilizing potassium triiodide, and the like.
[Preparation Method 1] (Step c) As shown in the following scheme 6 : Rs''= 41* (E') -- n-COOY- /C3'C2' Su0 (IIs) Rs' c C (CH2) n-COOY' 3 HO (VIII) (Scheme6) a compound represented by the formula (IIs) (this compound is hereinafter simply referred to as"Compound (ITs)"), which corresponds to Compound (II) wherein G represents mesylate group, triflate group, or an arenesulfonate group, can be prepared by converting a compound represented by the formula (VIII) (this compound is simply referred to as"Compound (VIII) "), which is commercially available or can be prepared by a known method or a method similar thereto, into a sulfonic acid ester. In the formula of Compound (IIs), the group Su represents methanesulfonyl group, trifluoromethanesulfonyl group, or arenesulfonyl group of which aromatic ring may be substituted with one of T'or two or more of identical or different T1. Examples of the method for the conversion into sulfonic acid ester include a preparation method described in ordinary publications in the filed of chemistry, for example, Shin Jikken Kagaku Koza (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 14, p. 1793. Examples of the method include a method utilizing sulfonyl chloride, a method utilizing sulfonic anhydride, and the like.
[Preparation Method 2] (Step d) As shown in the following scheme 7: (Scheme7) a compound represented by the formula (Ib') wherein Y represents hydrogen atom, and Rs, AR, and V on or in the aromatic ring (E) may be protected (this compound is hereinafter simply referred to as"Compound (Ib') "), which constitutes a part of the scope of Compound (I) of the present invention, can be prepared by hydrolyzing Compound (Ia') so as to convert the group OY'into hydroxyl group.
For the reaction of converting Compound (Ia') into Compound (Ib'), in general, the compound is preferably reacted in a base. Further, for the reaction of converting Compound (Ia') to Compound (Ib'), in general, the compound is preferably reacted in an inert medium that does not inhibit the reaction, preferably a polar solvent.
Examples of the base used in the above reaction include, for example, alkali metal bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide and potassium t-butoxide and organic bases such as triethylamine. As for amounts of the bases, generally 1 to 20 moles, preferably 1 to 10 moles, for alkali metal bases, or 1 to a large excess moles for organic bases based on Compound (Ia').
Examples of the polar solvent include water, methanol, ethanol, tetrahydrofuran, dioxane and the like, and these solvents may be used as a mixture as required. As the reaction temperature, an appropriate temperature of, for example, from room temperature to a refluxing temperature of solvent is chosen.
The reaction time is, for example, generally 0.5 to 72 hours, preferably 1 to 48 hours, when an alkali metal base is used, or generally 5 hours to 14 days when an organic base is used. Since progress of the reaction can be monitored by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) or the like, the reaction can generally be terminated appropriately so as to maximize the yield of Compound (Ib').
For collection of Compound (Ib') obtained as described above from the reaction solution as a free carboxylic acid, operations may preferably be carried out by, when the polar solvent is a water-soluble solvent, evaporating the solvent, neutralizing the residue with an inorganic acid such as aqueous hydrochloric acid, dissolving the residue in a water-insoluble solvent, then washing the solution with a weakly acidic aqueous solution, water or the like, and evaporating the solvent.
When the polar solvent is a water-insoluble solvent, operations may preferably carried out by neutralizing the reaction solution with an inorganic acid, washing the solution with a weakly acidic aqueous solution, water or the like, and then evaporating the solvent.
Further, when Compound (Ib') forms a salt with the base used after the reaction to give a solid, the salt of Compound (Ib') can be obtained by isolation and purification of the solid in a conventional manner.
When a protective group of hydroxyl group or amino group exists in the group AR', Rs'or V'in the aromatic ring (E') of Compound (Ia') prepared as described above, Compound (Ia') can be converted into Compound (I) of the present invention by removing the protective group during or after the preparation of Compound (Ia').
[Preparation Method 3] (Step e) As shown by the following scheme 8 : (Scheme8) a compound represented by the formula (Ic') [hereinafter simply referred to as "Compound (Ic')"] as Compound (I) of the present invention wherein the group Y represents Y", and Rs, AR, and V in the aromatic ring (E) may be protected, can be produced by esterifying the carboxyl group (COOH) of Compound (Ib') in a conventional manner. In the formula of Compound (Ib'), Y"represents a lower alkyl group having 1 to 4 carbon atoms, a-(CH2) mNRl8Rl9 group, or- C (Rzo) 20C (O) A3R21.
Examples of the method for producing Compound (Ic') include a method of allowing Compound (Ib') to react with an inorganic halide without solvent or in an inert solvent to convert the compound into an acid halide and then allowing the acid halide per se or the same dissolved in an inert solvent to react with an excess amount of hydroxide of the targeted Y". Examples of the inorganic halide used in this method include thionyl chloride, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride and the like, and thionyl chloride is a preferred example. Examples of an amount used include generally an equimolar to a large excess amount, preferably 1.5 to 5 moles based on Compound (Ib').
Examples of the inert solvent used in this reaction include, for example, halogenated hydrocarbons such as dichloromethane, chloroform and 1, 2- dichloroethane, ethers such as tetrahydrofuran and dioxane, and benzene compounds such as benzene, toluene, xylene and chlorobenzene. These solvents can be used, for example, each alone or as a mixed solvent. In order to promote the reaction, a catalytic amount of N, N-dimethylformamide may be added. As a reaction temperature, an appropriate temperature of from room temperature to a refluxing temperature of the solvent is generally chosen. Examples of the reaction time include generally 0.5 to 24 hours, preferably 1 to 6 hours.
Examples of the inert solvent used for the reaction with hydroxide of the targeted Y"include, for example, halogenated hydrocarbons such as dichloromethane, chloroform and 1, 2-dichloroethane, ethers such as tetrahydrofuran and dioxane, and benzene compounds such as benzene, toluene, and xylene. The reaction can also be performed with an excess amount of the hydroxide of the targeted Y"without using a solvent. As the reaction temperature, an appropriate temperature of from-10°C to room temperature is chosen.
Examples of the reaction time include generally 0.5 to 24 hours, preferably 0.5 to 6 hours.
Other methods for producing Compound (Ic') include, for example, the "esterification using an alcohol"described in Shin Jikken Kagaku Koza (edited by the Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 14, p. 1002, "esterification using an 0-alkylating agent", ibid, the same volume, p. 1002, "esterification using an alkyl halide", ibid, the same volume, p. 1008,"esterification reaction using a dehydrating agent", ibid, vol. 22, p. 45 and the like.
When hydroxyl group or amino group reactive under the aforementioned reaction conditions or inhibiting the reactions exists in AR', Rs'or V'in the aromatic ring (E'), this substituent is preferably protected.
When a protective group of hydroxyl group or amino group exist in AR', Rs' or V'in the aromatic ring (E') of the compound (Ic') prepared as described above, such a protecting group can be eliminated during or after the preparation of Compound (Ic') to convert the compound into Compound (I) of the present invention.
[Preparation Method 4] As shown in the following scheme 9 : Rs'C5=C6, (E') z AR' (Id') 5= RsX5 Rs'-.., ,- /COOY' p41 AR,... AR (Scheme9) UHZ) 2-COOY' 4--fa compound represented by the formula (Id') (hereinafter this compound is simply referred to as"Compound (Id') ") as Compound (I) of the present invention wherein n in the methylene moiety is an integer of 2, and wherein Rs, AR, and V in the aromatic ring (E) may be protected, can also be prepared by the method shown below.
[Preparation Method 4] (Step f) Compound (Id') can be prepared by reducing the double bond of a compound represented by the formula (IX) (hereinafter this compound is simply referred to as "Compound (IX) ") using a reduction reaction described in ordinary publications in the filed of chemistry. Examples of the reaction include a method of converting the double bond of Compound (IX) into a single bond by hydrogenation using a hydrogen source such as hydrogen gas, ammonium formate, and hydrazine hydrate in a single solvent or a mixed solvent of alcoholic-type solvents such as methanol, ester'type solvents such as ethyl acetate in the presence of a catalyst such as palladium/carbon powder, platinum oxide (PtO2), and activated nickel.
When hydroxyl group or amino group reactive under the aforementioned reaction conditions or inhibiting the reactions exists in AR', Rs'or V'in the aromatic ring (E'), this substituent is preferably protected.
When a protective group of hydroxyl group or amino group exist in AR', Rs' or V'in the aromatic ring (E') of the compound (Id') prepared as described above, such a protecting group can be eliminated during or after the preparation of Compound (Id') to convert the compound into Compound (I) of the present invention.
[Preparation Method 4] (Step g) Compound (IX) can be prepared from a compound represented by the formula (III) [hereinafter this compound is simply referred to as"Compound (III)"].
Examples of the preparation method include a method utilizing the Horner-Emonds reaction described in Shin Jikken Kagaku Koza (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 14, p. 238. Specifically, the compound can be obtained by reacting Compound (III) with a commercially available dialkylphosphonoacetic acid ester in an inert solvent, for example, an alcohol-type solvent such as methanol and ethanol or ether-type solvent such as tetrahydrofuran and dimethoxyethane in the presence of a base such as sodium hydride and sodium alkoxide. As the reaction temperature, an appropriate temperature of from-10°C to a refluxing temperature of a solvent is generally chosen, and preferred examples include a temperature of from 0°C to room temperature. The reaction time is generally 1 to 16 hours, preferably 2 to 8 hours. Since progress of the reaction can be monitored by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) or the like, the reaction can generally be terminated appropriately so as to maximize the yield of Compound (IX).
[Preparation Method 4] (Step a) As shown in the following scheme 10 : Rs', C5'=, CE'M-CHO -CHO c I), CHO 00 4-a N, r F-')/ "" c31-C2, AR (III) G (Scheme Compound (III) can be prepared by introducing the substituent AR'into a compound represented by the formula (X) [hereinafter this compound is simply referred to as "Compound (X)"] according to any of the methods described in the step a-1 of the preparation method 1 mentioned above.
[Preparation Method 5] As shown in the following scheme 11 : , s, Rs, C. COOH CN 2 \. AR (ive') Rsw 5 C /back AR' (Scheme1 a compound represented by the formula (Ie') [hereinafter this compound is simply referred to as"Compound (Ie')"], as Compound (I) of the present invention wherein n in the methylene moiety is an integer of 1, Y represents hydrogen atom, and Rs, AR, and V in the aromatic ring (E) may be protected, can also be prepared by the method shown below.
[Preparation Method 7] (Step d) Specifically, Compound (Ie') can be prepared by hydrolyzing nitrile group of a compound represented by the formula (XI) [hereinafter this compound is simply referred to as"Compound (XI)"] into carboxyl group according to a method similar to the method shown in the step d of the preparation method 2 mentioned above.
When a protective group of hydroxyl group or amino group exist in AR', Rs' or V'in the aromatic ring (E') of the compound (Ie') prepared as described above, such a protecting group can be eliminated during or after the preparation of Compound (Ie') to convert the compound into Compound (I) of the present invention.
[Preparation Method 5] (Step h) Compound (XI) can be produced from Compound (III) mentioned above.
For example, Compound (III) is reacted with a trimethylsilyl cyanide using a Lewis acid, particularly zinc iodide, as a catalyst in an inert solvent such as tetrahydrofuran as described in Jikken Kagaku Koza, 4th Edition (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd. ), vol. 20, p. 445. Then, the reduction reaction using a hydrosilane described in Jikken Kagaku Koza, 4th Edition (edited by Chemical Society of Japan, published by Maruzen Co. , Ltd.), vol.
26, p. 197 is performed. Examples of the method of the reduction reaction include a method of performing the reduction with a hydrosilane such as triethylsilane and a protonic acid such as trifluoroacetic acid or a Lewis acid such as boron trifluoride in a halogenated solvent such as dichloromethane.
The preparation method of Compound (I) is not limited to the methods described herein. For example, the compounds of the present invention can be produced by modifying or converting a substituent of a compound serving as a precursor of the compounds according to a method or a combination of methods described in ordinary publications in the filed of chemistry.
Examples of the preparation method for Compound (I) of the present invention which contains an asymmetric carbon in the substituent Rs include a method of using a starting material in which a moiety corresponding to the asymmetric carbon in the substituent Rs is already optically active, which is commercially available (or can be prepared by a known method or a method similar thereto). A method is also available in which the compound of the present invention or a precursor thereof is separated as an optically active isomer in a conventional manner. Examples of such method include, for example, a method utilizing high performance liquid chromatography (HPLC) using a chiral column, a method comprising condensation with an optically active regent to form a diastereomer, successive separation and purification, followed by decomposition.
When a precursor is separated to obtain an optical isomer, optically active Compound (I) of the present invention can then be prepared by performing the aforementioned preparation methods.
When Compound (I) of the present invention contains an acidic functional group such as carboxyl group or phenolic hydroxyl group, the compound can be converted into pharmaceutically acceptable salt (e. g. , inorganic salts with sodium, ammonia and the like, or organic salts with triethylamine and the like) by a known means. For example, when an inorganic salt is to be obtained, it is preferable to dissolve Compound (I) of the present invention in water containing at least 1 equivalence of hydroxide, carbonate, bicarbonate or the like corresponding to a desired inorganic salt. For the reaction, an inactive water-miscible organic solvent such as methanol, ethanol, acetone, and dioxane may be mixed. For example, by using sodium hydroxide, sodium carbonate, or sodium hydrogencarbonate, a solution of sodium salt can be obtained.
When Compound (I) of the present invention contains a basic functional group such as amino group, or when Compound (I) of the present invention contains an aromatic ring which itself has properties of base (e. g. , pyridine ring), the compound can be converted into a pharmaceutically acceptable salt (e. g. , salt with inorganic acids such as hydrochloric acid and sulfuric acid, or salts with organic acids such as acetic acid and citric acid) by a known means. For example, when an inorganic salt is to be obtained, it is preferable to dissolve Compound (I) of the present invention in water containing at least 1 equivalence of a desired inorganic acid. For the reaction, an inactive water-miscible organic solvent such as methanol, ethanol, acetone, and dioxane may be mixed. For example, by using hydrochloric acid, a solution of hydrochloride can be obtained.
When a solid salt is desired, a solution may be evaporated, or a water- miscible organic solvent having polarity to some extent, such as butanol or ethyl methyl ketone, can be added to obtain a solid salt thereof.
The various compounds disclosed by the present invention can be purified by known methods such as recrystallization, and variety of chromatography techniques (column chromatography, flash column chromatography, thin layer chromatography, high performance liquid chromatography).
Compound (I) of the present invention and pharmaceutically acceptable salts thereof have an action of suppressing the production of both of prostaglandins and leukotrienes. The action of suppressing the production of prostaglandins and/or leukotrienes includes, for example, an action of suppressing PGE2 production, observed when cultured cells of MG-63 which is a human osteosarcoma cell line are stimulated with IL-1 ß and/or PGD2 and LTB4 production observed when cultured cells of RBL-2H3 which is a rat mastocytoma cell line are stimulated with IgE, by 10% or more, preferably 30% or more, most preferably 50% or more, compared with a positive control at a concentration of the compound not having cytotoxicity. As for a mode of action at a molecular level, it is considered that the compound of the present invention inhibits both of COX-1 and/or COX-2, which produce prostaglandins, and 5-LO, which produces leukotrienes. It is also considered that the compound of the present invention suppresses the production of arachidonic acid by inhibiting enzymatic activity of type 2A, 4, or 5 PLA2 involved in prostaglandin and leukotrien production.
It is considered that, in these molecular action mechanisms, Compound (I) of the present invention inhibits the enzymatic activity of type 4 PLA2. For the judgment, for example, the enzyme inhibitory action against type 4 PLA2 can be examined, and known methods for measuring the enzymatic activity of type 4 PLA2 are preferably utilized [Clark et al. , Proceeding of National Academy of Science USA (Proc. Natl. Acad. Sci. USA), 1990, vol. 87, p. 7708 ; Gronich et al., Biochemical Journal (Biochem. J. ), 1990, vol. 271, p. 37 ; Clark et al., Cell, 1991, vol. 65, p. 1043 ; Kramer et al. , Journal of Biological Chemistry (J. Biol. Chem), 1991, vol. 266, p. 5268]. The type 4 PLA2 inhibitory action of the compounds of the present invention can be elucidated by employing these methods.
Compounds (I) of the present invention and pharmaceutically acceptable salts thereof inhibited mouse inflammatory edema, allergic edema, acetic acid writhing reaction, and rat adjuvant arthritis by oral administration at a dose of 0. 1 to 500 mg/kg, and caused no death of the mice by oral administration at a dose of 500 mg/kg/day for 3 days. Therefore, they are safe compounds as drugs for mammals, preferably humans, pets or companion animals such as dogs and cats, and farm animals, and they are useful substances as active ingredients of medicaments. Preferred examples of the medicaments for mammals, preferably humans, pets or companion animals such as dogs and cats, and farm animals include agents for prophylactic and/or therapeutic treatment of various conditions, various diseases, and pathological conditions in which an acute or chronic inflammatory reaction resulted from production of prostaglandin and/or leukotriene is observed, specifically inflammatory diseases, allergic diseases, autoimmune diseases, and pain.
More specifically, the conditions or diseases include arthritis, chronic rheumatoid arthritis, malignant rheumatoid arthritis, juvenile rheumatoid arthritis, Felty's syndrome, adult Still's disease, osteoarthritis, synovitis, gout, slack of artificial joint implant, fervescence, common cold, algesia, burn, thermal injury, keloplasty, menstrual pain, dysmenorrhea, menstrual cramp, allergic reaction, allergic contact hypersensitivity, allergic rhinitis, pollinosis, allergic conjunctivitis, hypersensitivity pneumonitis, allergic bronchopulmonary mycosis, emphysema, acute respiratory distress syndrome, asthma, bronchitis, chronic obstructive pulmonary disease, chronic bronchitis, pulmonary emphysema, diffuse panbronchiolitis, respiratory obstruction, graft versus host syndrome, urticaria, ultraviolet radiation dermatitis, atopic dermatitis, cancer, myelogenous leukemia, sarcomata, brain tumor, cachexia, tissue ulcer, digestive ulcer, gastritis, acute and chronic pancreatitis, regional enteritis, ulcerative colitis, diverticulitis, recurrent gastroenteric disorder, gastroenteric bleeding, inflammatory bowel disease, Crohn's disease, intestinal tract type Behcet's disease, infectious enteritis, ischemic enteritis, radiation enteritis, drug-induced enteritis, irritable bowel syndrome, hepatic diseases (hepatopathies, liver failures) such as acute hepatitis, fulminant hepatitis, chronic hepatitis, hepatic cirrhosis, fatty liver, alcoholic liver injury, drug liver injury (drug-induced hepatitis), congestive hepatitis, autoimmune hepatitis, primary biliary cirrhosis and hepatic porphyria, coagulation, anemia, ankylosing spondilitis, restenosis, periodontosis, epidermolysis bullosa, atherosclerosis, aortic aneurysm, periarteritis nodosa, congestive cardiac failure, arrhythmia, myocardial infarction, cerebral infarction, attack, cerebral ischemia, head injury, spinal cord injury, myelopathic muscular atrophy, neuralgia, neurodegenerative disease, Alzheimer's disease, Lewy body disease, Shy-Drager syndrome, Reye's syndrome, progressive supranuclear palsy, progressive multifocal leukoencephalopathy, normal pressure hydrocephalus, subacute sclerosing panencephalitis, frontal lobe type dementia, acute anterior poliomyelitis (poliomyelitis), poliomyelitis neurosis, viral encephalitis, Creutzfeldt-Jakob disease, Kuru disease, bovine spongiform encephalopathy (mad cow disease), scrapie, epilepsy, cerebral amyloid angiopathy, autoimmune disease, Huntington's disease, Parkinson's disease, migraine, depression, mania, manic-depressive psychosis, hereditary cerebellar ataxia, peripheral neuropathy, glaucoma, pain, gingivitis, postoperative pain, amyotrophic lateral sclerosis, osteoporosis, multiple sclerosis, ocular angiogenesis, cornea damage, macular degeneration, conjunctivitis, abnormal wound healing, sprain or strain of muscle or joint, tendinitis, skin disease, psoriasis vulgaris, pustular psoriasis, erythroderma psoriaticum, arthritic psoriasis, myasthenia gravis, multiple myositis, myositis, bursitis, diabetes mellitus, tumor invasion, tumor growth, tumor metastasis, cornea scar, scleritis, immunodeficiency disease, pachydermia, eosinophilic fasciitis, sepsis, endotoxin shock, premature delivery, hypoprothrombinemia, hemophilia, thyroiditis, sarcoidosis, Behcet's syndrome, hypersensitivity, renal disease, rickettsial infectious disease, protozoal disease, reproduction disease, sepsis shock and the like. Other specific conditions and diseases include toothache, pain after tooth extraction, back or low back pain, periarthritis humeroscapularis, cervico-omo-brachial syndrome, tenosynovitis, acute upper respiratory inflammation, herpes zoster, fibrosis, pulmonary fibrosis, pneumoconiosis, chronic interstitial pneumonia, granulomatous interstitial pneumonia, fibrosing interstitial pneumonia, renal fibrosis, nephropyelitis, various types of secondary contracted kidney, glomerular nephritis, chronic nephritis, glomerulosclerosis, hepatic fibrosis, cardiac fibrosis after myocardial infarction, idiopathic cardiomyopathy, pancreatic sclerosis, pancreatic fibrosis, pancreatolithiasis, Takayasu's arteritis, chronic thyroiditis, dermatomyositis, multiple myositis, myelofibrosis, Banti disease, retroperitoneal fibrosis, various radiation injuries and the like. Further, the medicament comprising Compound (I) of the present invention as an active ingredient can be used for the aforementioned conditions or diseases of mammals, preferably humans, pets or companion animals such as dogs and cats or farm animals together with or in combination with one or more kinds of other prophylactic or therapeutic drugs.
Examples of the drugs that can be used together or in combination include, for example, the following drugs : immunomodulation-type antirheumatic drugs and antimetabolite used as therapeutic drugs for rheumatoid arthritis, specifically, gold preparations, bucillamine, lobenzarit, salazosulfapyridine, methotrexate, azathiopurin, mizoribine, leflunomide, tacrolimus, cyclosporin and the like and preparations containing the same; anti-cytokine antibody preparations directed to cytokines such as interleukin (IL) 1, IL-6, and tumor necrosis factor (TNF)-a or preparations of soluble receptors for those cytokines, which are biological preparations, specifically, infliximab, etanercept and the like and preparations containing the same ; steroid preparations, specifically, dexamethasone, betamethasone, prednisolone, fluticasone, beclometasone and the like and preparations containing the same ; bronchodilators used as therapeutic agents for chronic bronchial asthma, specifically, salmeterol and salbutamol, which are adrenalin B 2 stimulants, ipratropium, which is an anticholinergic drug, and the like and preparations containing the same ; therapeutic drugs for allergic diseases, for example, theophyline, which is a xanthine analogue drug, and the like, fexoquinadine, epinastatine, cetirizine, ketotifen, disodium cromoglycate, pemirolast and the like, which are antiallergic agents, fexoquinadine, cetirizine and the like, which are antihistaminic agents, and preparations containing the same ; irinotecan, 5-fluorouracil and the like, which are antitumor agents, and preparations containing the same. Further, the medicament comprising Compound (I) of the present invention as an active ingredient is used, for example, together with or in combination with radiotherapy.
In order to use Compound (I) of the present invention or pharmaceutically acceptable salts thereof for the medicaments described above, an effective amount of Compound (I) of the present invention or a pharmaceutically acceptable salt thereof, per se, may be used, or the substance may be mixed with a pharmaceutically acceptable carrier to form a pharmaceutical composition. The carrier may be, for example, a suspending agent such as carboxymethylcellulose, or purified water, physiological saline or the like, if desired. Other known carriers can also be used. Examples include a method of dissolving Compound (I) of the present invention or a pharmaceutically acceptable salt thereof in purified water containing 0.5% carboxymethylcellulose and using the solution.
Examples of formulations for preparing the aforementioned pharmaceutical composition include tablet, powder, granule, syrup, suspension, capsule, and injection. For the manufacture of these formulations, various carriers suitable for these preparations are used. For example, examples of the carrier for oral preparations include excipients, binders, lubricants, fluid accelerators, and colorants.
When the compound of the present invention is formulated as a parenteral preparation such as an injection, water for injection, physiological saline, glucose aqueous solution, vegetable oil for injection, propylene glycol, polyethylene glycol and the like can generally be used as a diluent. Disinfectants, antiseptics, stabilizers, isotonic agents, soothing agents and the like may be further added, as required.
When the compound of the present invention is administered to a mammal, e. g. , human, the compound can be administered in the form of a tablet, a powder, a granule, a suspension, a capsule or the like. The compound can also be parenterally administered in the form of a suppository, a gel, a lotion, an ointment, a cream, or a spray. A dose thereof varies depending on a disease to be applied, administration route, age, weight, degree of symptom of a patient and the like.
Examples of the dose include generally an administration at a dose of 1 to 1,000 mg per day for an adult once to three times a day. Every day administration for a period of several days to two months is commonly applied. The daily dose and the administration period may be increased or decreased depending on symptoms of a patient.
Fibrosis, which is a disease characterized by fibrosing of tissues, is known as a severe disease which is often mortal. Fibrosing of tissues is caused by proliferation of interstitial cells, which represented by fibroblasts, and production of extracellular matrix such as collagen. Fibrosing is considered a repair mechanism against tissue affections in organs. Excessive fibrosing causes fibrosing diseases of organs, and further progression of fibrosing causes sclerotic diseases. Many of such sclerotic diseases are intractable, progressive and irreversible. Although fibrosing varies in various organs, etiological hypotheses of fibrosing have many similarities. That is, a certain inflammatory lesion precedes, and in its healing process, various kinds of cytokines and growth factors are produced mainly from immunocompetent cells and platelets as well as interstitial cells such as fibroblasts themselves involved in the healing, and activated to cause deposition of extracellular matrix (Takehara, Molecular Medicine, 2001, vol. 38, p. 854).
Among fibroses, pulmonary fibrosis is one of the representative diseases.
Pulmonary fibrosis is a disease in which disruption of alveolar structure is caused by chronic inflammation and increase of collagenic fibers in alveolar walls, and which eventually leads to respiratory failure and death. For example, pulmonary fibrosis occurs following infectious pneumonia and the like. Examples of the infectious pneumonia include severe acute respiratory syndrome (SARS) and influenzal pneumonia. It has been reported that, in SARS, in particular, severe inflammation is caused in pulmonary stroma, and as a result, it highly likely to develop into pulmonary fibrosis (Antonino et al. , Radiology, 2003). In addition, pulmonary fibrosis is also caused by various medicaments.
In recent years, with increase of medicaments used for diagnosis, prophylactic and therapeutic treatments of various kinds of diseases, drug-induced pulmonary fibrosis caused by such drugs is increasing. Drug-induced pulmonary fibrosis is a severe disease that eventually leads to death, and it causes serious problems in therapeutic treatments of various diseases. Therefore, prophylactic and therapeutic treatments of drug-induced pulmonary fibrosis constitute a particularly important subject of concern.
Against drug-induced pulmonary fibrosis, steroid therapy is currently used.
However, effective rate of the steroid therapy is low and the effect is only partial and transient, and thus lesions often remain [Igaku no Ayumi, 2001, vol. 197, p. 313]. Further, side effect of steroid agents and acute aggravation due to decrease of doses or termination of their administrations are also often observed, which remains clinically far unsatisfactory level.
As a recent finding, it was reported that administration of pirfenidone was effective against pulmonary fibrosis in clinical tests in the United States (Raghu et al. , American Journal of Respiratory and Critical Care Medicine, 1999, vol. 159, p. 1061) and Japan (Nagai et al., Internal Medicine, 2002, vol. 41, p. 1118).
However, development of novel prophylactic and/or therapeutic agents highly effective for these diseases is desired at all events.
The medicament provided by the present invention is useful as a medicament containing a type 4 PLA2 inhibitor as an active ingredient for prophylactic and/or therapeutic treatment of fibrosis, preferably pulmonary fibrosis, further preferably drug-induced pulmonary fibrosis.
As described above, fibrosis, in particular, pulmonary fibrosis, is a severe disease and is an important object of prophylactic and/or therapeutic treatment.
As for pulmonary fibrosis, more than 100 kinds of factors including toxic gases and various medicaments have been elucidated as the causes of early alveolopathy. As described above, with the increase of medicaments used for diagnosis, prophylactic and therapeutic treatments of various kinds of diseases, drug-induced pulmonary fibrosis caused by such drugs is increasing.
As for drug-induced pulmonary fibrosis, causality between expression of pathological conditions such as coughing, difficulty of breathing, or fervescence and the administration of medicaments is suspected, and it is considered that a diffuse interstitial shadow appears on a thoracic X-ray photograph simultaneously with or slightly after the administration of medicaments.
As medicaments reported to cause drug-induced pulmonary fibrosis, anticancer agents, anti-rheumatic agents, immunosuppressants, antibiotics, chemotherapeutants, antihypertensive agents, diuretics, anti- inflammatory/analgesic agents, biologics, Chinese medicines are known (Inooka et al. , Therapeutics, 1995, vol. 29, p. 1295). Typical medicaments are shown in Table 1.
Table 1 Classification Examples of agent 1) Anticancer agent, Peplomycin, bleomycin, cychlophosphamide, nitrosourea, immunosuppressant busulfan, methotrexate, azathioprine, mitomycin-C, tegafur, carmofur, tegafur/uracil preparation, cisplatin, doxorubicin, 6-mercaptopurine, daunomycin, vincristine, vinblastine, vindesine, procarbazine, neocarzinostatin, melphalan, thiotepa, nimustine, cytarabine, zinostatin stimalamer, chlorambucil, carmustine, lomustine, semustine, teniposide, etoposide, Taxol, taxotere, irinotecan, gefitinib, tamoxifen and the like. 2) Antihypertensive a-methyldopa, trichlormethiazide, hydrochlorothiazide, agent, diuretic enalapril, hexamethonium, mecamylamine, pentolinium, practolol, pindolol, propranolol, acebutolol, hydralazine 3) Antibiotic, Cephem antibiotics (cephaloridine, cephalothin, chemotherapeutant cephalexin, cefradine, cefazolin, cefaclor, cefmenoxime, cefmetazole, cefoperazone, cefotiam, cefroxadin, ceftizoxime, latamoxef and the like), tetracyclines (minocycline, oxycycline), antituberculous agents (isoniazid, paraaminosalicylic acid, rifampicin, streptomycin), penicillin antibiotics (ampicillin, piperacillin, vastcillin, pentcillin, amoxicillin), aminoglycoside antibiotics (streptomycin), macrolide antibiotics (midecamycin), phosphomycin, aminoglycosides (tobramycin, Micromycin), new quinolone drugs (enoxacin, ofloxacin, norfloxacin), antifungal agents (amphotericin) and the like 4) Others Inhalants (cromoglicic acid and the like), gold preparations (aurothiomalic acid and the like), psychotropic agents and nervines (aminotriptyline, diphenylhydantoin, carbamazepine, phenobarbital, valproate salt, imipramine, mephenesin, meprobamate), antiphlogistic and analgesics (naproxen, acetaminophen, acetylsalicylic acid, phenacetin, diclofenac, loxoprofen, fenbufen, nabumetone, aluminoprophen and the like), antiarrhythmic agents (amiodarone, procainamide, aprindine), antidiabetic agents (chlorpropamide), antithyroid agents (thiouracil), proteolytic enzymes (serrapeptidase), antiparkinsonic agents (levodopa, bromocriptine), antirheumatic agents (bucillamine, auranofin, actarit), sho-saiko-to, chai-ling-tang, rikkunshi-to, interferon, warfarin, salazosulfapyridine, dichloroferamide, fominoben, D-penicillamine, propylthiouracil, corticosteroid, flavoxate, allopurinol, ethoxysclerol and the like In therapeutic treatment of rheumatoid arthritis, for example, agents that cause pulmonary fibrosis at high frequency such as methotrexate and sodium aurothiomalate are used as disease-modifying antirheumatic drugs. Further, disease-modifying antirheumatic drugs that may cause pulmonary fibrosis at a relatively low frequency, such as actarit, bucillamine, auranofin, salazosulfapyridine, and D-penicillamine are also used. Although these disease- modifying antirheumatic drugs are useful agent in the rheumatoid arthritis treatment system, pulmonary fibrosis caused as a side effect is a factor of restricting use of these drugs. In recent years, methotrexate, in particular, has come to be used as an antirheumatic agent, and onset of pulmonary fibrosis that is also histopathologically called interstitial pneumonia as the side effect of methotrexate becomes a problem in the rheumatoid arthritis treatment system.
Further, in cancer therapy, cychlophosphamide, Taxol, etoposide, cisplatin, vincristine, vinblastine, irinotecan, gefitinib, and bleomycin are useful as anticancer agents. However, because all of these anticancer agents cause pulmonary fibrosis that is also histopathologically called as interstitial pneumonia as a side effect at a high frequency, they have a problem in the therapeutic treatment system. Bleomycin, gefitinib, irinotecan, and cisplatin are used for therapeutic treatment of lung cancer. However, if patients with lung cancer develop pulmonary fibrosis, the condition is most likely for the patients to be fatal.
Among these drugs, bleomycin suffers from a problem that it causes pulmonary fibrosis at a high frequency.
Preferred objects of application of the medicament of present invention are drug-induced pulmonary fibroses caused by these drugs.
In present invention, the type 4 PLA2 inhibitor is not particularly limited so long as the inhibitor has type 4 PLA2 inhibitory activity. For example, known type 4 PLA2 inhibitors can be chosen. Examples of the known type 4 PLA2 inhibitors include the following inhibitors : the compounds described in U. S. Patent No. 5,462, 954, preferably 2-phenyl-4-ethyl-5- [6- (2H-tetrazol-5-yl)-6- methylheptyloxy] phenol, 8-propyl-7- {3- [4- (4-fluorophenyl)-2-ethyl-5- hydroxyphenyloxy] propyloxy}-3, 4-dihydro-2H-1-benzopyran-2-carboxylic acid, and 2- {3- [3- ([5-ethyl-2-hydroxy (l, 1'-bip henyl)-4-yl] oxy) propyloxy]-2- propylphenyloxy} propionic acid ; the compounds described in W099/43654, preferably 4- (1-benzhydryl-6-chloro-lH-indol-3-ylmethyl)-3-methoxybenzoic acid ; the compounds described in W098/33797, preferably N-14- (biphenyl-2-ylmethyl- isobutylamino)-1- [2- (4-fluorobenzoyl) benzoyl] pyrrolidin-2-ylmethyl}-3- [4- (2,4- dioxothiazolidin-5-ylidenemethyl) phenyl] acrylamide and the like ; the compounds described in WO01/30387, preferably N- [2- (2,4-difluorobenzoyl) benzoyl]-4- tritylsulfanylpyrrolidin-2-ylmethyl}-4- (2, 4-dioxothiazolidin-5-ylidenemethyl) benzoic acid amide and the like; the compounds described in W099/15129, preferably 4-{4- [2- (2- [bis (4-chlorophenyl) methoxy] ethylsulfonyl) ethoxy] phenyl}-1, 1, 1-trifluoro-2- butanone and the like ; the compounds described in W098/05637, preferably 1- {2- [4- (carboxymethyl) phenoxy] ethyl}-3-dodecanoylindole-2-carboxylic acid and the like ; the compounds described in Japanese Patent Unexamined Publication (Kokai) No.
2002-80368, preferably 4-methyl-2-oxo-5- (5, 6,7, 8-tetrahydronaphthalen-2- yl) oxazolidine-3-carboxylic acid (6-methoxytetrahydropyran-2-yl) amide, 4-methyl-2- oxo-5- (4-methylphenyl) thiazolidine-3-carboxylic acid (tetrahydropyran-2-yl) amide and the like ; and the type 4 PLA2 inhibitors selected from the compounds described in W098/08818, the compounds described in W099/43651, the compounds described in W099/43672, the compounds described in W003/048122, the compounds described in W095/10508, the compounds described in W097/05135, the compounds described in Japanese Patent Unexamined Publication No. 7-126166, the compounds described in Japanese Patent Unexamined Publication No. 7-224076, the compounds described in Japanese Patent Unexamined Publication No. 7-224076, the compounds described in Japanese Patent Unexamined Publication No. 2000- 119292, the compounds described in Japanese Patent Unexamined Publication No.
2000-109432, the compounds described in Japanese Patent Unexamined Publication No. 7-223997, the compounds described in the U. S. Patent No. 5,994, 398, the compounds described in WO00/27824, the compounds described in Japanese Patent Unexamined Publication No. 2000-38380, the compounds described in WOOO/71118, the compounds described in Japanese Patent No. 3107613, the compounds described in W003/031414, the compounds described in U. S. Patent No. 5,453, 443, and the compounds described in W002/038575. Examples further include the following known type 4 PLA2 inhibitors described in references arachidonyl trifluoromethyl ketone (Street et al. , Biochemistry, 1993, vol. 32, p. 5935) ; methyl arachidonyl fluorophosphate (Kennedy et al. , Mediators of Inflammation, 1994, vol.
3, p. 337) ; (3-lactam derivatives (Burke et al. , J. Enzyme Inhibition, 1998, vol. 13, p. 195) ; choline derivatives (Burke et al. , J. Biol. Chem. , 1999, vol. 274, p. 18864) ; 1, 3-disubstituted propan-2-one derivatives, especially 4- [3- (4-decyloxyphenyloxy)-2- oxopropyloxy] benzoic acid (Connolly et al. , J. Med. Chem. , 2002, vol. 45, p. 1348) ; Surfactin (Kim et al. , Biochem. Pharmacol. , 1998, vol. 55, p. 975) ; 1,1, 1- trifluorononadeca-10, 13,16-trien-2-one and 1, 1, 1-trifluorononadeca-10, 13-dien-2- one (Amandi-Burgermeister et al. , Eur. J. Pharmacol. , 1997, vol. 326, p. 237); and 2- oxoamide derivatives (Kokotos et al. , J. Med. Chem. , 2002, vol. 45, p. 2891).
In the present invention, preferred examples of type 4 PLA2 inhibitor further include the compounds represented by the aforementioned formula (I) and pharmacologically acceptable salts thereof. Various combinations of the compounds represented by the formula (I) and pharmacologically acceptable salts thereof described in the specification can also be arbitrarily chosen.
When a medicament comprising a type 4 PLA2 inhibitor as an active ingredient is used as a prophylactic and/or therapeutic agent for fibrosis, as for Compound (1) of the present invention, for example, Compound (I) of the present invention or a pharmaceutically acceptable salt thereof, per se, may be used in an effective amount, or the substance may be used after preparation of a pharmaceutical composition in the form of solid, liquid or gel by mixing the substance with a pharmaceutically acceptable carrier. As for the pharmaceutically acceptable carrier, known information and the information about carriers described in this specification can be referred to. As for known type 4 PLA2 inhibitors, a known type 4 PLA2 inhibitor or a pharmaceutically acceptable salt thereof, per se, may be used in an effective amount, or as mentioned above, the inhibitors may be used after preparation of a pharmaceutical composition by mixing the inhibitor with a pharmaceutically acceptable carrier.
It would be readily understood by those skilled in the art that progression- preventing agents, that is used for preventing progression of pathological conditions, occasionally fall within the scope of the agent for prophylactic and/or therapeutic treatment of the present invention.
Examples of the dosage form for preparation of the aforementioned pharmaceutical composition, tablet, powder, granule, syrup, suspension, capsule, inhalant, injection, and the like, and in order to prepare the compositions, various carriers are used depending on the type of the composition. Examples of the carrier for oral agents include, for example, excipients, binders, lubricants, flowability improvers, and colorants. When an inhalant is prepared (examples of administration method include a method of inhaling powder of the pharmaceutical composition or a solution obtained by dissolving or suspending the pharmaceutical composition in a solvent, per se, a method of inhaling mist of the composition prepared by using a sprayer called atomizer or nebulizer), the preparation the aforementioned pharmaceutical composition in the form of solid can be referred to for preparation of a powder for the inhalation, and a powder obtained is preferably further made into micropowder. When the composition is inhaled as a liquid, preferred examples of the preparation method include a method of dissolving a solid pharmaceutical composition, which is prepared by referring to the above explanation, in distilled water or a suitable solvent to obtain a solution of medicament upon use, and a method of preparing a liquid pharmaceutical composition prepared by referring the above explanation to obtain a solution of medicament. As for a size of the aforementioned powder or mist of a solution of a medicament to be inhaled, a particle size may be suitable for inhalation. For example, an upper limit is preferably 100, u m or less, further preferably 50, u m or less, most preferably 10 ju m or less. A lower limit is not particularly limited, and a smaller particle size is more preferred. When an injection and the like are prepared, distilled water for injection, physiological saline, glucose solution, vegetable oil for injection, propylene glycol, polyethylene glycols and the like can generally be used as diluents. Further, antimicrobial agents, antiseptics, stabilizers, isotonic agents, soothing agents, and the like may be added, as required.
When the aforementioned prophylactic and/or therapeutic agent is administered, a suitable dosage form can be chosen and administered via a suitable route. For example, the agent can be orally administered in the form of a tablet, a powder, a granule, a syrup, a suspension, or a capsule. The agent can also be administered via transairway route in the form of an inhalant. Further, the agent can be administered subcutaneously, intradermally, intravascularly, intramuscularly or intraperitoneally in the form of injection including a drip infusion. Furthermore, the agent can be transmucosally administered in the form of a sublingual agent or a suppository, and can be transdermally administered in the form of a gel, a lotion, an ointment, a cream, or a spray.
A dose thereof varies depending on the dosage form, and the age, weight, degree of symptoms of a patient and the like. Examples of the dose include generally an administration at a dose of 1 to 1,000 mg per day for an adult once to three times a day. Every day administration for a period of several days to two months is commonly applied. The daily dose and the administration period may be increased or decreased depending on symptoms of a patient.
As for the application of the aforementioned prophylactic and/or therapeutic agent, the agent may be administered to patients with pulmonary fibrosis as explained above. In addition, the prophylactic and/or therapeutic agent of the present invention containing a type PLA2 inhibitor as an active ingredient may preferably be administered after the administration of, most preferably immediately after the administration of an agent, which may possibly induces pulmonary fibrosis as an adverse reaction. Furthermore, as for the administration time, the prophylactic and/or therapeutic agent of the present invention may be administered simultaneously with an agent which may possibly induces pulmonary fibrosis as an adverse reaction, or the agent of the present invention may be administered beforehand.
Examples The present invention will be further specifically explained with reference to examples. However, the scope of the present invention is not limited to the following examples. In the examples, for thin layer chromatography (TLC), Precoated Silica Gel 60 F254 (produced by Merck, product number: 5715-1M)) was used. After development with chloroform: methanol (1 : 0 to 1: 1), acetonitrile: acetic acid: water (200: 1: 1 to 100: 4: 4) or ethyl acetate: hexane (1: 0 to 0: 1), spots were observed by UV irradiation (254 nm) or color development with ninhydrine or dinitrophenylhydrazine solution in hydrochloric acid. For drying organic solvent, anhydrous magnesium sulfate or anhydrous sodium sulfate was used. As for column chromatography, the indication of"Quad"means use of Quad 1 preparative chromatography system (produced by Biotage), and one or several columns selected from cartridge columns KP-Sil-12M, 40S and 40M produced by the same manufacturer were used depending on the amount of sample. For flash column chromatography, Silica gel 60N (spherical shape, neutral, 40 to 100, u m, produced by Kanto Chemicals) was used. Preparative thin layer chromatography (hereinafter abbreviated as"PTLC") was performed by using one or several plates of PLC Plate Silica Gel 60 F254 (20 x 20 cm, thickness: 2 mm, concentration zone : 4 cm, produced by Merck, product number: 13793-1M) were used depending on the amount of sample.
The indication of"LCMS"means that mass spectrum was measured by liquid chromatography-mass spectrometry (LC-MS). Platform-LC type mass spectrometry apparatus (produced by Micromass) was used as the mass spectrometer, and the measurement was performed by the electrospray ionization (ESI) method. As a liquid chromatography apparatus, an apparatus produced by GILSON was used. As a separation column, Mightysil RP-18 GP 50-4.6 (produced by Kanto Chemicals) was used. Elution was generally performed at a flow rate of 2 mllminute, and Solution A = water [containing 0. 1% (v/v) acetic acid] and Solution B = acetonitrile [containing 0.1% (v/v) acetic acid] were used as solvents.
In the tables mentioned below, data indicated by"LCMS"mean data of liquid chromatography-mass spectrometry spectra. In the columns of"Mass", data of mass spectrometry were shown (the indication"N. D" means that no molecular ion peak was detected). In the columns of"method", elution conditions of the liquid chromatography are described. In the columns of"RTime", retention times in the liquid chromatography are shown. For the indication of retention time in the liquid chromatography, the indication"A"for elution condition means that measurement was performed by elution with a linear gradient of 5 to 100% (v/v) Solution B from 0 minute to 5 minutes and then with 100% Solution B until 6 minutes. Similarly, the indication"B"for elution condition means that measurement was performed by elution with 30% (v/v) Solution B from 0 minute to 0.5 minute, then with a linear gradient of 30 to 95% (v/v) Solution B from 0.5 minute to 4 minutes and then with 95% (v/v) Solution B until 6 minutes. For the compounds with the indication C in the columns of elution conditions, data of mass spectrometry measured by fast atomic bombardment mass spectrometry (FAB-MS) using JEOL-JMS-SX102 (produced by JEOL Co. , Ltd. ) were mentioned in the columns of"Mass". Further, for the compounds with the indication D in the elution conditions, an apparatus manufactured by Waters Ltd. was used as a liquid chromatography apparatus. As a column for separation, Develosil C30-UG-5 (50 x 4.6 mm, Nomura Kagaku Co. , Ltd. ) was used. Measurement was performed under elution condition with a linear gradient of 5 to 98% (v/v) Solution B from 0 minute to 4 minutes and then with 100% Solution B until 6 minutes.
In the columns indicated as"Exp.", compound numbers are shown. When the tables include a column indicated as"position", substituting positions of substituents are indicated in the column. The abbreviations used in the tables have the following meanings. n: normal, i : iso, s: secondary, t: tertiary, c: cyclo, D : di, Me: methyl, Et: ethyl, Pr: propyl, Bu: butyl, Pen: pentyl, Hex: hexyl, Hep: heptyl, Ph: phenyl, Bn: benzyl, Py: pyridyl, Indan: indanyl, Ac: acetyl, CHO: formyl, COOH : carboxyl, N02 : nitro, DMA : dimethylamino, NH2 : amino, CF3: trifluoromethyl, F: fluoro, Cl: chloro, Br: bromo, OMe : methoxy, OH : hydroxy, TFA: trifluoroacetyl, S02 : sulfonyl, CO: carbonyl, Nap: naphthyl, Ind : lH-indolyl, lHIdz : 1H-indazolyl, 2HIdz: 2H-indazolyl, Bzt: benzothiazole, 2ABzt: 2-aminobenzothiazole, BF : benzofuranyl, BT : benzo [b] thienyl, Qu : Quinolyl, IQ: isoquinolyl The numbers given before the substituents indicate substituting positions.
The numbers given with hyphens before abbreviations of aromatic rings indicate substituting positions of the aromatic rings. (S) indicates optically active substances with S-configuration, and (R) indicates optically active substances with R-configuration. Representative examples of the substituents shown in the tables with abbreviations are listed in Table 2 mentioned below.
Table 2 Structure abbreviation abbreviation Structure cPenMeO 2EtBuO--Iro 3DMeBuO aO cPenO 1 cHexO zu ce t o 2-Indano (4FPh) EtO (4DMAPh) EtO . F 2 o 2 (PhO) EtO F 4 (OMe) BnC 2-Nap Ne » N St N @ 3-Qu N The manufacturers of the regents used may sometimes be indicated with the following abbreviations.
TCI: Tokyo Kasei Kogyo Co. , Ltd., Ald : Aldrich Co. , KANTO: Kanto Kagaku, WAKO: Wako Pure Chemical Industries, Ltd., LANC : Lancaster Synthesis, MAYB: Maybridge, plc.
[Example A-1] Synthesis of methyl 3- (4-hydroxyphenyl) propionate (Intermediate 1) A solution obtained beforehand by adding thionyl chloride (18.3 ml, WAKO) dropwise to methanol (250 ml) and mixing the mixture under ice cooling was added dropwise with a solution of 3- (4-hydroxyphenyl) propionic acid (16. 6g, TCI) in methanol (50 ml) under ice cooling, stirred for 30 minutes, warmed to room temperature, and further stirred for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and then extracted with diethyl ether (200 ml). The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine.
The organic layer was dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate 1,17. 95 g).
Synthesis of methyl 3- (4-cyclopentylmethyloxyphenyl) propionate (Intermediate 2) A solution of cyclopentane methanol (4.05 ml, Ald) in anhydrous tetrahydrofuran (abbreviated as"THF"hereinafter, 40 ml) was added with triethylamine (6.49 ml, WAKO), added dropwise with methanesulfonyl chloride (3.48 ml, WAKO) under ice cooling, and stirred for 30 minutes. The reaction mixture was added with water (50 ml), and extracted with diethyl ether (80 ml x 2).
The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. A solution obtained beforehand by adding 60% sodium hydride (1.15 g, KANTO) to a solution of Intermediate 1 (4.50 g) in N, N-dimethylformamide (abbreviated as"DMF"hereinafter, 35 ml) under ice cooling and stirring the solution for 15 minutes was added with a solution of the aforementioned residue in DMF (10 ml) under ice cooling. The reaction mixture was stirred for 15 minutes, then warmed to room temperature, stirred for 45 minutes, and further stirred at 60°C for 15 hours. The reaction mixture was added with water (100 ml) and diethyl ether (200 ml) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : isopropyl ether = 9: 1) to obtain the title compound (Intermediate 2,5. 58 g).
Synthesis of methyl 3- (3-bromo-4-cyclopentylmethyloxyphenyl) propionate (Compound No. A-1) A solution of Intermediate 2 (1.31 g) in acetonitrile (50 ml) was added with N-bromosuccinimide (hereinafter abbreviated as"NBS", 979 mg, KANTO), stirred at room temperature for 2 hours, then warmed to 40°C, and stirred for 3 hours.
The reaction mixture was concentrated under reduced pressure, then added with ethyl acetate (200 ml) and washed successively with saturated aqueous ammonium chloride, 5% aqueous sodium sulfite, saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Compound No. A- 1,1. 69 g).
[Example A-2] Synthesis of 3- (3-bromo-4-methoxyphenyl) propionic acid (Intermediate 3) According to the procedure described in the synthesis method of Compound No. A-1 provided that the reaction was carried out under ice cooling for 30 minutes and at room temperature for 3 hours, 3- (4-methoxyphenyl) propionic acid (27.0 g, TCI) and NBS (29.4 g) were reacted and treated to obtain the title compound (Intermediate 3,38. 1 g).
Synthesis of 3- (3-bromo-4-hydroxyphenyl) propionic acid (Intermediate 4) According to a procedure described in a literature (Carreno, M. C. , J. Org.
Chem. , 1995, vol. 60, p. 5328), a 1 M solution of boron tribromide in methylene chloride (200 ml, Fluka) was added dropwise with a solution of Intermediate 4 (23.5 g) in methylene chloride (200 ml) at-78°C, warmed to room temperature after 30 minutes, and further stirred for 1.5 hours. The reaction mixture was poured into ice water (750 ml), and stirred at room temperature for 1 hour. The reaction mixture was added with diethyl ether (750 ml) ) for extraction. The organic layer was added with 2 N aqueous sodium hydroxide (250ml x 2) for extraction, and then the aqueous layer was made acidic with 5 N aqueous hydrochloric acid under ice cooling, and extracted with diethyl ether (375 ml x 2) again. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate 4,23. 5 g).
Synthesis of methyl 3- (3-bromo-4-hydroxyphenyl) propionate (Intermediate 5) According to the procedure described in the synthesis method of Intermediate 1 provided that the purification was performed by flash column chromatography (hexane : ethyl acetate = 4: 1), Intermediate 4 (21.15 g) and thionyl chloride (15.0 ml) were reacted and treated in methanol to obtain the title compound (Intermediate 5,20. 36 g).
Synthesis of methyl (3-bromo-4-cyclohexylmethyloxyphenyl) propionate (Compound No. A-2) A solution of Intermediate 5 (1.29 g) in DMF (25 ml) was added with potassium carbonate (0. 86 g) and bromomethylcyclohexane (1.05 ml, TCI), stirred under argon atmosphere at room temperature for 2 hours, then warmed to 60°C, and stirred for 17 hours. The reaction mixture was poured into ice water, and extracted with isopropyl ether (200 ml). The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : isopropyl ether = 9: 1) to obtain the title compound (Compound No. A-2,1. 45 g).
[Example A-5] Synthesis of methyl 3- (3-bromo-4-cyclopentyloxyphenyl) propionate (Compound No.
A-5) A solution of Intermediate 5 (4.50 g) in DMF (20 ml) was added with 60% sodium hydride (440 mg, KANTO) under ice cooling. The reaction mixture was stirred for 10 minutes, then added with bromocyclopentane (1.61 ml, TCI), warmed to room temperature, stirred for 1.5 hours, then warmed to 60°C, and further stirred for 16 hours. The reaction mixture was added with water (50 ml) and isopropyl ether (300 ml) ) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane: isopropyl ether = 7: 1) to obtain the title compound (Compound No. A-5,2. 50 g).
[Example A-6] Synthesis of methyl 3- (3-bromo-4-cyclohexyloxyphenyl) propionate (Compound No.
A-6) A solution of Intermediate 5 (2.06 g), triphenylphosphine (hereinafter abbreviated as"PhsP", 6. 28 g, WAKO) and cyclohexanol (2.53 ml, WAKO) in anhydrous THF (60 ml) was added dropwise with a 40% solution of diisopropylazodicarboxylic acid ester in toluene (hereinafter abbreviated as"40% DIAD", 11.35 ml, WAKO) under ice cooling over 10 minutes. The reaction mixture was stirred for 10 minutes, then warmed to room temperature, and stirred for 18.5 hours. The reaction mixture was added with water (50 ml) and ethyl acetate (200 ml) ) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: isopropyl ether = 8: 1) to obtain the title compound (Compound No. A-6,2. 35 g).
[Example A-20] Synthesis of methyl 3- (3-bromo-5-chloro-4-hydroxyphenyl) propionate (Intermediate 6) A solution of Intermediate 5 (516mg) in chloroform (5 ml) was added with sulfuryl chloride (177 u 1), and stirred at room temperature for 21 hours. The reaction mixture was poured into aqueous saturated sodium hydrogencarbonate (20 ml), and extracted with ethyl acetate. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10 : 1) to obtain the title compound (Intermediate 6,290mg).
Synthesis of methyl 3- (3-bromo-5-chloro-4-cyclopentylmethyloxyphenyl) propionate (Compound No. A-20) According to the procedure described in the synthesis method of Compound No. A-6 provided that the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 30: 1), Intermediate 6 (278 mg), PhsP (747 mg), cyclopentane methanol (308 A 1), and 40% DIAD (1.34 ml) were reacted and treated to obtain the title compound (Compound No. A-20,337mg).
[Example A-21] Synthesis of ethyl 3- (3-fluoro-4-methyloxyphenyl) acrylate (Intermediate 7) A solution of 3-fluoro-4-methoxybenzaldehyde (2.20 g, Ald) in 1,2- diethoxyethane (5 ml) was added with ethyl diethylphosphonoacetate (3.12 ml, TCI) and added with 60% sodium hydride (624mg) under ice cooling. After being stirred for 10 minutes, the reaction mixture was warmed to room temperature, and stirred for 5 hours. The reaction mixture was added with ethyl acetate (90 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (Quad, hexane : ethyl acetate = 10: 1) to obtain the title compound (Intermediate 7,3. 16 g).
Synthesis of ethyl 3- (3-fluoro-4-methoxyphenyl) propionate (Intermediate 8) A solution of Intermediate 7 (3.01 g) in ethyl acetate (50 ml) and methanol (25 ml) was added with 10% palladium/carbon (300 mg, Merck), and stirred at room temperature for 2 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Intermediate 8,3. 02 g).
Synthesis of 3- (3-fluoro-4-methoxyphenyl) propionic acid (Intermediate 9) A solution of Intermediate 8 (2. 97 g) in methanol (40.0 ml) was added with 2 N aqueous sodium hydroxide (15.0 ml) and stirred at 60°C for 16 hours. The reaction mixture was concentrated under reduced pressure, then made acidic with aqueous 5% hydrochloric acid under ice cooling, and extracted with ethyl acetate (200 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate 9,2. 40 g).
Synthesis of 3- (3-fluoro-4-hydroxyphenyl) propionic acid (Intermediate 10) A pyridine/hydrochloric acid complex prepared by mixing pyridine (30 ml) and concentrated hydrochloric acid (30 ml) and heating the mixture at 190°C for 1 hour was added with Intermediate 9 (2.40 g) and stirred at 190°C for 1.5 hours.
The reaction mixture was poured into 1 N hydrochloric acid (100 ml) cooled with ice, and extracted with. ethyl acetate (200 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate 10,1. 98 g).
Synthesis of methyl 3- (3-fluoro-4-hydroxyphenyl) propionate (Intermediate 11) According to the procedure described in the synthesis method of Intermediate 1, Intermediate 10 (1.77 g) and thionyl chloride (1.65 ml) were reacted and treated in methanol to obtain the title compound (Intermediate 11,1. 85 g).
Synthesis of methyl 3- (3-bromo-5-fluoro-4-hydroxyphenyl) propionate (Intermediate 12) According to the procedure described in the synthesis method of Compound No. A-1 with the modifications that the reaction was carried out for 2 hours under ice cooling, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 10: 1), Intermediate 11 (1.84 g) and NBS (1.74 g) were reacted and treated to obtain the title compound (Intermediate 12,1. 74 g).
Synthesis of methyl 3- (3-bromo-4-cyclopentylmethyloxy-5-fluorophenyl) propionate (Compound No. A-21) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 22 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 50: 1), Intermediate 11 (310 mg), tributylphosphine (hereinafter abbreviated as"nBusP", 405 u 1, WAKO) instead of Ph3P, cyclopentane methanol (176, u 1), and N, N, N', N'-tetramethylazodicarboxamide (hereinafter abbreviated as "TMAD", 279 mg, TCI) instead of 40% DIAD were reacted and treated to obtain the title compound (Compound No. A-21, 386 mg).
[Example A-24] Synthesis of 4-cyclopentyloxy-3-methylbenzaldehyde (Intermediate 13) According to the procedure described in the synthesis method of Compound No. A-2 with the modifications that the reaction was carried out for 16 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 9 : 1), 4-hydroxy-3-methylbenzaldehyde (283 mg, TCI), potassium carbonate (578 mg) and bromocyclopentane (430, u 1) were reacted and treated to obtain the title compound (Intermediate 13,350 mg).
Synthesis of ethyl 3- (4-cyclopentyl-3-methylphenyl) acrylate (Intermediate 14) According to the procedure described in the synthesis method of Intermediate 7 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 9 : 1), Intermediate 13 (342 mg), ethyl diethylphosphonoacetate (408 u 1) and 60% sodium hydride (82 mg) were reacted and treated to obtain the title compound (Intermediate 14,450 mg).
Synthesis of ethyl 3- (4-cyclopentyl-3-methylphenyl) propionate (Intermediate 15) According to the procedure described in the synthesis method of Intermediate 8, Intermediate 14 (446 mg) and 10% palladium/carbon (20 mg) were reacted and treated under hydrogen gas atmosphere to obtain the title compound (Intermediate 15, 439 mg).
Synthesis of ethyl 3- (3-bromo-4-cyclopentyl-5-methylphenyl) propionate (Compound No. A-24) According to the procedure described in the synthesis method of Compound No. A-l, Intermediate 15 (437 mg) and NBS (320 mg) were reacted and treated to obtain the title compound (Compound No. A-24, 545 mg).
[Example A-25] Synthesis of 3-bromo-4- (t-butyldimethylsilyloxy)-5-methoxybenzaldehyde (Intermediate 16) A solution of 3-bromovanillin (1.16 g, TCI) in anhydrous DMF (20 ml) was added with imidazole (408 mg, TCI), added dropwise with a solution of 4-(N, N- dimethylamino) pyridine (25 mg) and t-butyldimethylsilyl chloride (904 mg, TCI) in DMF (15 ml) under ice cooling, stirred 30 minutes, then warmed to room temperature, and further stirred 3 hours. The reaction mixture was added with water (100 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 9 : 1) to obtain the title compound (Intermediate 16,1. 75 g).
Synthesis of ethyl 3- [3-bromo-4- (t-butyldimethylsilyloxy)-5-methoxyphenyl] acrylate (Intermediate 17) According to the procedure described in the synthesis method of Intermediate 7 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 9 : 1), Intermediate 16 (910 mg), ethyl diethylphosphonoacetate (530 u 1) and 60% sodium hydride (120 mg) were reacted and treated to obtain the title compound (Intermediate 17,937 mg).
Synthesis of ethyl 3- [3-bromo-4- (t-butyldimethylsilyloxy)-5- methoxyphenyl] propionate (Intermediate 18) According to the procedure described in the synthesis method of Intermediate 8, Intermediate 17 (945 mg) and 10% palladium/carbon (95 mg) were reacted and treated under hydrogen gas atmosphere to obtain the title compound (Intermediate 18,760 mg).
Synthesis of ethyl 3- (3-bromo-4-hydroxy-5-methoxyphenyl) propionate (Intermediate 19) A solution of Intermediate 18 (750 mg) in THF (50 ml) was added with a 1 M solution of tetrabutylammonium fluoride in THF (5 ml, TCI), and stirred for 1.5 hours. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate (30 ml), and extracted with ethyl acetate (50 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 4: 1) to obtain the title compound (Intermediate 19,542 mg).
Synthesis of ethyl 3- (3-bromo-4-cyclopentyloxy-5-methoxyphenyl) propionate (Compound No. A-25) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 16 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 7: 1), Intermediate 19 (400 mg), Ph3P (1.31 g), cyclopentanol (450, u 1), and TMAD (860 mg) were reacted and treated to obtain the title compound (Compound No. A-25,376 mg).
[Example A-26] Synthesis of methyl 3- (3-bromo-4-cyclopentylmethyloxy-5-nitrophenyl) propionate (Compound No. A-26) A solution obtained beforehand by adding 70% nitric acid (3.9 ml) to acetic anhydride (30 ml) under ice cooling and stirring the mixture for 10 minutes was added with a solution of Compound No. A-1 (5.12 g) in acetonitrile (25 ml) at-15°C over 15 minutes, and stirred further for 15 minutes. The reaction mixture was poured into 1 N aqueous sodium hydroxide (500 ml) containing ice, and extracted with diethyl ether (300 ml x 2). The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10: 1) to obtain the title compound (Compound No. A-26,3. 68 g).
[Example A-31] Synthesis of methyl 3- (3-bromo-4-phenoxyphenyl) propionate (Compound No. A-31) A solution of Intermediate 5 (3.08 g) in anhydrous N-methylpyrrolidone (9.5 ml, WAKO) was successively added with cesium carbonate (3.58 g, WAKO), iodobenzene (1.4 ml, TCI), dipivaloylmethane (0.12 ml, TCI) and copper (I) chloride (275 mg, WAKO), and stirred 120°C for 16 hours under argon gas atmosphere. The reaction mixture was added with t-butyl methyl ether (25 ml), and insoluble solids were removed by filtration. The filtrate was washed successively with 2 N aqueous hydrochloric acid and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane: ethyl acetate = 1: 10) to obtain the title compound (Compound No. A-31, 1.00 g).
[Example B-96] Synthesis of methyl 3- (3-bromo-4-methoxyphenyl) propionate (Intermediate 20) According to the procedure described in the synthesis method of Intermediate 1 provided that the purification was performed by flash column chromatography (hexane: ethyl acetate = 6: 1), Intermediate 3 (1.60 g) and thionyl chloride (1.44 ml) were reacted and treated in methanol to obtain the title compound (Intermediate 20,1. 63 g).
Synthesis of methyl 3- (3-bromo-4-methoxy-5-nitrophenyl) propionate (Intermediate 21) A solution of Intermediate 20 (3.20 g) in acetic anhydride (25 ml) was added with potassium nitrate (1.30 g) under ice cooling and stirred for 10 minutes, and the solution was added dropwise with concentrated sulfuric acid (730, u 1) over 10 minutes. The reaction mixture was stirred for 10 minutes for 10 minutes at the same temperature, then warmed to room temperature, and further stirred for 30 minutes. The reaction mixture was poured into 1 N aqueous sodium hydroxide (250 ml) containing ice, and extracted with isopropyl ether (200 ml x 2). The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 10: 1) to obtain the title compound (Intermediate 21,2. 73 g).
Synthesis of 3- (3-bromo-4-methoxy-5-nitrophenyl) propionic acid (Intermediate 22) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1 hour, Intermediate 21 (12.73 g) and 2 N aqueous sodium hydroxide (40 ml) were reacted and treated to obtain the title compound (Intermediate 22,11. 53 g).
Synthesis of 3- (3-bromo-4-hydroxy-5-nitrophenyl) propionic acid (Intermediate 23) According to the procedure described in the synthesis method of Intermediate 4 provided that the reaction was carried out for 2 hours, Intermediate 22 (11.53 g) and a 1 M solution of boron tribromide in methylene chloride (100 ml) were reacted and treated to obtain the title compound (Intermediate 23,10. 68 g).
Synthesis of methyl 3- (3-bromo-4-hydroxy-5-nitrophenyl) propionate (Intermediate 24) According to the procedure described in the synthesis method of Intermediate 1 provided that the reaction was carried out for 17.5 hours, Intermediate 23 (10. 68 g) and thionyl chloride (8.06 ml) were reacted and treated to obtain the title compound (Intermediate 24,8. 27 g).
Synthesis of methyl 3- [3-bromo-4- (indan-2-yloxy)-5-nitrophenyl] propionate (Compound No. B-96) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 15 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 19 : 1), Intermediate 24 (151 mg), Ph3P (260 mg), 2-hydroxyindane (133 mg, TCI) and 40% DIAD (470, u 1) were reacted and treated to obtain the title compound (Compound No. B-96, 192 mg).
Example B-99] Synthesis of methyl 3- (3-amino-5-bromo-4-cyclopentyloxyphenyl) propionate (Compound No. B-99) A solution of Compound No. A-28 (416 mg) in a mixture of THF (5 ml) and methanol (5 ml) was added with Raney 2800 nickel (230 mg, Ald) and stirred at room temperature for 6 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 5 : 2) to obtain the title compound (Compound No. B-99, 143 mg).
[Example B-103] Synthesis of methyl 3- [4-benzyloxy-5-bromo-3- (2, 2,2- trifluoroacetylamino) phenyl] propionate (Compound No. B-103) A solution of Compound No. B-100 (58.7 mg) in methylene chloride (2 ml) was added with triethylamine (76 u 1), added dropwise trifluoroacetic anhydride (91 u 1, TCI) under ice cooling, stirred for 30 minutes, then warmed to room temperature, and further stirred for 2 hours. The reaction mixture was added with water (5 ml), and extracted with methylene chloride (20 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 3: 1) to obtain the title compound (Compound No. B-103,59. 1 mg).
[Example B-105] Synthesis of methyl 3- [4-benzyloxy-5-bromo-3- (N-methylamino) phenyl] propionate (Compound No. B-105) A solution of Compound No. B-100 (105 mg) in DMF (3 ml) was added with 60% sodium hydride (20 mg) under ice cooling, and stirred for 10 minutes. This reaction mixture was added dropwise with methyl iodide (32 It 1), stirred for 10 minutes, then warmed to room temperature, and further stirred for 2 hours. The reaction mixture was poured into water, and added with ethyl acetate (30 ml) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 6: 1) to obtain the title compound (Compound No. B-105, 17 mg).
[Example B-109] Synthesis of 3- [4-benzyloxy-5-bromo-3- (N, N-dimethylamino) phenyl] propionic acid (Compound No. B-109) A solution of Compound No. B-100 (105 mg) in DMF (3 ml) was added with 60% sodium hydride (40 mg) under ice cooling, and stirred for 10 minutes. This reaction mixture was added dropwise with methyl iodide (300/ l), stirred for 10 minutes, then warmed to room temperature, and further stirred for 16 hours. The reaction mixture was poured into water, and added with ethyl acetate (30 ml) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 6: 1) to obtain the title compound (Compound No. B-109,88 mg).
[Examples B-113 and B-114] Syntheses of 3- (3-bromo-4-cyclopentyloxy-5-hydroxyphenyl) propionic acid (Compound No. B-113) and 3- (5-acetoxy-3-bromo-4-cyclopentyloxyphenyl) propionic acid (Compound No. B-114) A solution of Compound No. B-99 (415 mg) in acetic acid (1.5 ml) was added with 20% sulfuric acid (1.0 ml). This reaction mixture was added dropwise with an aqueous solution (0.5 ml) of sodium nitrite (78 mg) over 10 minutes, while the temperature of the reaction mixture was maintained below 10°C, and further stirred for 5 minutes. This reaction mixture was added dropwise to a solution of sodium acetate (348 mg) in acetic acid (3.5 ml) heated and stirred at 100°C beforehand over 5 minutes, and further stirred for 10 minutes with heating. The reaction solution was poured into ice water (50 ml), and extracted with isopropyl ether (100 ml x 2). The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10: 1) to obtain the title compounds (Compound No. B-113, 47mg and Compound No. B-114,105 mg).
[Example B-117] Synthesis of methyl 3- (3, 5-dibromo-4-cyclopentylmethyloxyphenyl) propionate (Compound No. B-117) A solution of Intermediate 1 (670 mg) in acetonitrile (30 ml) was added with NBS (990 mg), stirred at room temperature for 2 hours, then warmed to 40°C, and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure, then added with ethyl acetate (100 ml), and washed successively with saturated aqueous ammonium chloride, 5% aqueous sodium sulfite, saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 18 hours under ice cooling, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 10: 1), the residue was reacted with Ph3P (1460 mg), cyclopentane methanol (560 mg) and 40% DIAD (2.6 ml) and treated to obtain the title compound (Compound No. B-117,710 mg).
Examples A-1 to A-33] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-A-1. The compounds were prepared according to the preparation methods of the compound numbers (e. g.,"A-1") or the intermediate numbers (e. g. ,"Int 2") shown in the columns of"Syn"in the tables. "Int"means an intermediate compound number. When the preparation required a plurality of steps, a plurality of compound numbers or intermediate compound numbers are mentioned in the columns of"Syn". For example, an indication of"Int 2, A-1"in a column of"Syn"means that"the compound is prepared from a compound prepared according to the procedure described in the synthesis method of Intermediate 2 according to the procedure described in the synthesis method of Compound No. A- 1."When the compounds were synthesized according to the procedure described in the synthesis method of Compound No. A-6, TMAD or di-t-butyl azodicarboxylate (hereinafter abbreviated as"DBAB") was sometimes used instead of 40% DIAD. Ex' RX G O Table-A-1 Exp. Rx'O Y, method RTime Mass A-1 cPenMeO Me H Br A-1 C A-2 cHexMeO Me H Br A-2 C A-3 iBuO Me H Br A-2 A 5. 34 N. D A-4 2EtBuO Me H Br A-2 A-5 cPenO Me H Br A-5 C A-6 cHexO Me H Br A-6 C A-7 cHepO Me H Br A-6 A-8 BnO Me H Br A-2 A-9 lPhEtO Me H Br A-2 A-10 2FBn0 Me H Br A-2 A-11 4FBnO Me H Br A-2 A-12 2CIBnO Me H Br A-13 4CIBnO H Br A-2 A 4. 85 N. D A-14 4MeBnO Me H Br A-2 A-15 Me H Br A-2 A-16 2 (4DMAPh) EtO Me H Br A-6 A-17 2 (PhO) EtO Me H Br A-6 A 5. 04 N. D A-18 1 (2FPh) EtO Me H Br A-6 A-19 Me H Br A-6 A 4. 82 N. D A-20 cPenMeO Me Cl Br A-20 A-21 cPenMeO Me F Br A-21 A-22 cPenO Me F Br A-21| C A-23 cHexO Me F Br A-21 A-24 cPenO Et Me Br A-24 A 5. 82 N. D A-25 cPenO OMe Br A-25 A-26 cPenMeO Me N02 Br A-26| C A-27 cHexMeO Me N02 Br A-26 A-28 cPenO Me N02 Br A-26 C A-29 cHexO Me N02 Br A-26 A-30 2-IndanO Me NO2 Br A-26 A 5. 03 N. D A-31 PhO Me H Br A-31 A 5. 15 D A-32 4CIPhO Me H Br A-31 A 5. 47 N. D A-33 4MeOPhO Me H Br 5. 02 N. D [Examples B-1 to B-119] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-B-1 to Table B-3. zxt , Rx- G O Table-B-1 i nn r Exp. Rx'O Y'Zx'G method Mass B-1 nPrO Me H Br B-2 Me H Br A-2 B-3 Me H Br A-6 B-4 iPenO Me H Br A-6 B-5 1, 3DMeBuO Me H Br A-6 B-6 2MeBuO Me H Br A-6 B-7 Me H Br A-6 B-8 A-6 B-9 2, 3DMeBuO Me H. Br A-6 B-10 cPenO Me H Cl A-6 C B-11 cPenO Me H Br A-6 B-12 3Me, cPenO Me H Br A-6 B-13 cHexO Me H Br A-6 B-14 cHexO Me H Br A-6 B-15 cHexO Me H Br A-6 C B-16 cHexO Me H Br A-6 B-17 2, 3DMe, cHexO Me H Br A-6 B-18 cHexO Me H Br A-6 C l B-19 3, 5DMe, cHexO Me H Br A-6 B-20 Me H Br A-6 B-21 Me H Br A-6 0 B-22 4to Me H Br A-6 H B-23 1 H Br A-6 B-24 (S) 1 Me H Br B-25 BenzhydrylO Me H Br A-6 B-26 H Br A-6 C 391 (M++1) 0 B-27 Meo _ ° Me Br A-6 F B-28 2Ph, 1 Me H Br A-6 B-29 2Ph, 2MeEtO Me H Br A-6 B-30 2 (2FPh), 1 Me H Br A-6 B-31 2 (3CF3Ph), 1 H Br B-32 3PhBuO Me H Br A-6 B-33 50Me-2-IndanO Me H Br A-6 B-34 5, Me H Br A-6 B-35 5F-2-IndaneO Me H Br A-6 B-36 1-IndaneO Me H Br A-6 B-37 mu Me H Br A-6 O Y'Table-B-2 viz B-38 j Me H Br A-6 B-39 B-39 B-40 Me H Br A-6 C B-41 3MeBnO Me H Br A-6 B-42 3, 5DMeBnO Me H Br A-6 B-43 4tBuBnO Me H Br A-6 B-44 2CF3BnO Me H Br A-6 B-45 4CF3BnO Me H Br A-6 B-46 3 (CF30) BnO Me H Br A-6 B-47 4 (CF30) BnO Me H Br A-6 B-48 4 (nBuO) Me H Br A-6 S B-49 Me 406 (M++1) B-50 Me H B-51 2, 4DFBnO Me H Br A-6 B-52 4Br, 2FBnO Me H Br A-6 B-53 2, 4DCIBnO Me H Br A-6 B-54 3, Me H Br A-6 B-55 2, Br A-6 B-56 2, 6DCIBnO Me H Br A-6 B-57 3, 5DCIBnO Me H Br A-6 B-58 2-NapMeO Me H Br A-6 C399 +1) B-59 1-NapMeO Me H Br A-6 B-60 _0 Me H Br A-6 B-61 Me H Br A-6 B-62 >° Me H Br A-6 C 339 (M++1) oll B-63 2PhBnO Me H Br A-6 B-64 4PhBnO Me H Br A-6 B-65 2PhEtO Me H Br A-6 B-66 2 (2MePh) EtO Me H Br A-6 B-67 2 (3MePh) EtO Me H Br A-6 B-68 2 (4MePh) EtO Me H Br A-6 B-69 2 (3FPh) EtO Me H Br A-6 B-70 2 Me H Br A-6 B-71 2 (2CF3Ph) EtO Me H Br A-6 B-72 2 (4CF3Ph) EtO Me H Br A-6 B-73 2 (20MePh) EtO Me H Br A-6 B-74 2 (2-Nap) EtO Me H Br A-6 C B-75 2 (3-Ind) EtO Me H Br A-6 s 0 B-76 Me H Br A-6 N B-77 B-78 2 (2CIPhO) Me H Br A-6 B-79 2 (4CIPhO) Me H Br jTable-B-3 0 B-80 "° Br A-6 C 407 (M++1) B-81 Me H Br A-6 B-82 Me H Br A-6 r B-83 r"""° Me H Br A-6 B-84 2 (PhS) EtO Me H 379 (M++1) B-85 2-BztO Me H Br A-6 B-86 (60Me-2-Bzt) O Me H Br A-6 B-87 cPenO Me Cl Br A-20 B-88 1 (4FPh) EtO Me CI Br B-89 1 Me F Br A-21 B-90 1 (4FPh) EtO Me F Br A-21 B-91 1 Et Me Br A-24 B-92 1 (4FPh) EtO Et Me Br A-24 B-93 1 Me OMe Br A-25 B-94 1 (4FPh) EtO Me OMe Br A-25 B-95 BnO Me N02 Br A-26 B-96 2-IndanO Me N02 Br A-26 A 4. 44 N. D B-97 50Me-2-IndanO Me N02 Br A-26 B-98 4CF3BnO Me N02 Br A-26 B-99 cPenO Me NH2 Br B-99 C B-100 BnO Me NH2 Br B-99 B-101 1 Me NH2 Br B-99 B-102 50Me-2-IndanO Me NH2 Br B-99 B-103 BnO Me NHTFA Br B-103 B-104 cPenO Me NHTFA Br B-103 C B-105 BnO Me NHMe Br B-105 B-106 cPenO Me NHMe Br B-105 C B-107 1 Me NHMe Br B-105 B-108 1 (4FPh) EtO Me NHMe Br B-105 B-109 BnO Me NMe2 Br B-109 B-110 cPenO Me NMe2 Br B-109 C B-111 1 Me NMe2 Br B-109 B-112 1 (4FPh) EtO Me NMe2 Br B-109 B-113 cPenO Me OH Br B-113 C B-114 cPenO Me COM Br B-114 B-115 1 (4FPh) EtO Me OH Br B-113 B-116 1 (4FPh) EtO Me COM Br B-114 B-117 cPenMeO Me Br. Br B-117 B-118 cPenO Me Br Br B-117 A 5. 98 N. D B-119 1 (4FPh) EtO Me Br Br B-117 [Example C-1] Synthesis of 3-bromo-4-cyclohexylmethyloxybenzaldehyde (Intermediate 25) According to the procedure described in the synthesis method of Compound No. A-2 provided that the purification was performed by flash column chromatography (hexane : isopropyl ether = 5: 1), 3-bromo-4-hydroxybenzaldehyde (17. 4 g), potassium carbonate (23.9 g) and bromomethylcyclohexane (36.2 ml) were reacted and treated to obtain the title compound (Intermediate 25,18. 7 g).
Synthesis of 4-cyclohexylmethyloxy-3- (naphthalen-2-yl) benzaldehyde (Compound No. C-1) A solution of 2-naphthaleneboronic acid (535 mg) in methanol (5.0 ml), Intermediate 25 (1.16 g), and 2 M aqueous sodium carbonate (0.9 ml) were added with toluene (10. 0 ml) and tetrakistriphenylphosphinepalladium (0) [hereinafter abbreviated as"(Ph3P) 4Pd"] (116 mg, Nakarai Tecs), and stirred at 80°C for 17 hours. The reaction mixture was added with ethyl acetate (100 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 10 : 1) to obtain the title compound (Compound No. C-1, 345 mg).
[Example D-10] Synthesis of 3-bromo-4-hydroxy-5-nitrobenzaldehyde (Intermediate 26) A solution of 3-bromo-4-hydroxybenzaldehyde (6.30 g) in acetic acid (45 ml) was added dropwise with 70% nitric acid (5.85 ml) on a water bath, then added with sodium nitrite (62 mg), and further stirred for 2 hours. The reaction mixture was poured into ice water (300 ml), and precipitates were taken by filtration, and washed with water (50ml x 3). The precipitates were dried under reduced pressure for 24 hours to obtain the title compound (Intermediate 26,5. 88 g).
Synthesis of 3-bromo-4-cyclohexylmethyloxy-5-nitrobenzaldehyde (Intermediate 27) According to the procedure described in the synthesis method of Compound No. A-2 provided that the purification was performed by flash column chromatography (hexane : ethyl acetate = 7: 1), Intermediate 26 (5.5 g), potassium carbonate (3.94 g) and bromomethylcyclohexane (3.94 ml) were reacted and treated to obtain the title compound (Intermediate 27,5. 2 g).
Synthesis of 4-cyclohexylmethyloxy-3- (naphthalen-2-yl)-5-nitrobenzaldehyde (Compound No. D-10) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 15 hours at 80°C, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 7: 1), Intermediate 27 (2.65 g), 2-naphthaleneboronic acid (3.01 g), 2 M aqueous sodium carbonate (7.5 ml) and (Ph3P) 4Pd (960 mg) were reacted and treated to obtain the title compound (Compound No. D-10, 2.96 g).
[Examples C-1 to C-8] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-C-1. zx Zx' Rx'-0 CHO AR Table-C-1 Rx'O Position RTime Mass C-1 cHexMeO 4 H-2-Nap C-2 cHexMeO 4 H-1-Nap 5 C-1 C-3 cHexMeO 4 H-20Me-6-Nap C-4 cHexMeO 4 H-5-Ind 5 C-1 C-5 cPenMeO 4 H-2-Nap C-6 cPenMeO 4 H-5-Ind 5 C-1 C-7 cPenO 5 C-1 C C-8 cPenO 4 5 C-1 C [Examples D-1 to D-29] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-D-1. zxw Rx'-0 ,-l 44 Table-D-1 2 Exp. Exp. Position PositonPosttion Postton method RTtme Mass D-1 cHexMeO 4 H-2-BT 3 C-1 D-2 cHexMeO 4 H-2-BF 3 C-1 D-3 cHexMeO 4 H-1 D-4 cHexMeO 4 H-5-1HIdz D-5 cHexMeO 4 H 3 C-1 D-6 2 (2FPh) EtO 4 H-2-Nap 3 C-1 D-7 2 (2FPh) EtO 4 H-5-Ind 3 C-1 D-8 2-IndanO 4 H-5-Ind 3 C-1 D D-9 2-IndanO 4 H-5-1HIdz 3 C-1 D-10 cPenMeO 4 N02 5 2-Nap 3 D-10 C D-11 cPenMeO 4 N02 5 5-Ind 3 D-10 D-12 cHexMeO 4 5 2-Nap 3 D-10 D-13 cHexMeO 4 N02 5 2-BF 3 D-10 D-14 cPenO 4 NO2 5 2-Nap 3 D-10 D-15 cPenO 5 5-Ind 3 D-10 C D-16 2 4 N02 5 2-Nap 3 D-10 D-17 2 (2FPh) 4 N02 5 5-Ind 3 D-10 D-18 2-IndanO 4 N02 5 5-Ind 3 D-10 D_l82_lndano D-19 2-IndanO 4 N02 5 1 3 D-10 A 3. 85 414 (M++1) D-20 cPenO 2 H-2-Nap D-21 cPenO 2 H-5-Ind 5 C-1 C D-22 cPenO 3 H-2-Nap 5 C-1 D-23 cPenO 3 H-5-Ind 5 C-1 D-24 cPenO 5 H 2 C-1 D-25 cPenO 5 H-5-Ind 2 C-1 D-26 cPenO 4 H 2 C-1. D-27 cPenO 4 H-5-Ind 2 C-1 D-28 cPenO 3 H 2 C-1 D-29 cPenO 3 H 2 C-1 [Example E-1] Synthesis of 5-bromo-2-cyclopentylmethyloxypyridine (Intermediate 28) A solution of potassium t-butoxid (550.6 mg, WAKO) in dehydrated THF (10 ml) was added with cyclopentane methanol (450 u 1), and then added with a solution of 2, 5-dibromopyridine (982.8 mg, TCI) in dehydrated THF (15 ml) under ice cooling. The reaction mixture was stirred for 30 minutes, then warmed to room temperature, and stirred for 11 hours. The reaction mixture was added with water (100 ml) and ethyl acetate (60 ml) for extraction. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine sequentially, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 15: 1) to obtain the title compound (Intermediate 28, 896 mg).
Synthesis of 2-cyclopentylmethyloxypyridine-5-carbaldehyde (Intermediate 29) A solution of Intermediate 28 (895 mg) in anhydrous THF (10 ml) was added dropwise with a 1.6 M solution of n-butyllithium in hexane (2.70 ml, Ald) over 5 minutes with cooling at'78°C under argon gas atmosphere, and stirred for 20 minutes. This reaction mixture was added with dehydrated DMF (330, u 1, WAKO) over 3 minutes, stirred for 30 minutes, then warmed to room temperature, and further stirred for 1 hour. The reaction mixture was added with water (10 ml), and extracted with ethyl acetate (30ml x 3). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10: 1) to obtain the title compound (Intermediate 29,1. 04 g).
Synthesis of ethyl 3- (2-cyclopentylmethyloxypyridin-5-yl) acrylate (Intermediate 30) According to the procedure described in the synthesis method of Intermediate 7 with the modification that the reaction was carried out for 1 hour, Intermediate 29 (450 mg), ethyl diethylphosphonoacetate (530 u 1) and 60% sodium hydride (120 mg) were reacted and treated to obtain the title compound (Intermediate 30,394 mg).
Synthesis of ethyl 3- (2-cyclopentylmethyloxypyridine-5-yl) propionate (Intermediate 31) According to the procedure described in the synthesis method of Intermediate 8 with the modifications that the reaction was carried out for 1 hour, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 15 : 1), Intermediate 30 (392 mg) and 10% palladium/carbon (30 mg) were reacted and treated to obtain the title compound (Intermediate 31,246 mg).
Synthesis of ethyl 3- (3-bromo-2-cyclopentylmethyloxypyridin-5-yl) propionate (Compound No. E-1) A solution of Intermediate 31 (5.20 g) in acetonitrile (50 ml) was warmed to 35°C, added dropwise with bromine (1.1 ml, WAKO), then added with NBS (3.72 g), and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, then added with ethyl acetate (200 ml), and washed successively with saturated aqueous ammonium chloride, 5% aqueous sodium sulfite, saturated aqueous sodium hydrogencarbonate and saturated brine.
The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 10 : 1) to obtain the title compound (Compound No. E-1, 6.51 g).
[Example E-7] Synthesis of 2-benzyloxy-5-bromopyridine (Intermediate 32) According to the procedure described in the synthesis method of Intermediate 28 provided that the reaction was carried out for 1 hour, potassium t- butoxide (3.13 g), benzyl alcohol (3.10 ml) and 2,5-dibromopyridine (4.79 g) were reacted and treated to obtain the title compound (Intermediate 32,5. 36 g).
Synthesis of 2-benzyloxypyridine-5-carbaldehyde (Intermediate 33) According to the procedure described in the synthesis method of Intermediate 29, Intermediate 32 (5.10 g), a 1.6M solution of n-butyllithium in hexane (15.5 ml) and dehydrated DMF (1.9 ml) were reacted and treated to obtain the title compound (Intermediate 33,2. 75 g).
Synthesis of ethyl 3- (2-benzyloxypyridin-5-yl) acrylate (Intermediate 34) According to the procedure described in the synthesis method of Intermediate 7, Intermediate 33 (2. 74 g), ethyl diethylphosphonoacetate (3.12 ml) and 60% sodium hydride (635 mg) were reacted and treated to obtain the title compound (Intermediate 34,2. 12 g).
Synthesis of ethyl 3- (2-hydroxypyridin-5-yl) propionate (Intermediate 35) According to the procedure described in the synthesis method of Intermediate 8 provided that the reaction was carried out for 2.5 hours, Intermediate 54 (2.12 g) and 10% palladium/carbon (120 mg) were reacted and treated to obtain the title compound (Intermediate 35,1. 26 g).
Synthesis of ethyl 3- (3-bromo-2-hydroxypyridin-5-yl) propionate (Intermediate 36) According to the procedure described in the synthesis method of Compound No. E-1 with the modifications that the reaction was carried out for 2.5 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 1 : 2), Intermediate 35 (1.23 g), bromine (340, u 1) and NBS (1.19 g) were reacted and treated to obtain the title compound (Compound No. 36,1. 42 g).
Synthesis of ethyl 3- [5-bromo-6- [(S)-l-phenylethyloxy] pyridin-3-yl] propionate (Compound No. E-7) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 11 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 4 : 1), Intermediate 36 (137 mg), PhsP (273 mg), (R)-l-phenylethanol (150 , u 1, TCI) and 40% DIAD (400 u 1) were reacted and treated to obtain the title compound (Compound No. E-7, 167 mg).
[Example E-13] Synthesis of ethyl 3- (5-bromo-6- (4-trifluoromethylbenzyloxy) pyridin-3-yl) propionate (Compound No. E-13) A solution of Intermediate 36 (71.5 mg) in chloroform (7 ml) was added with 4-trifluoromethylbenzyl bromide (109.2 mg, TCI) and silver carbonate (120 mg, WAKO), and stirred at room temperature for 11 hours under light shielding. The reaction mixture was filtered, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 6: 1) to obtain the title compound (Compound No. E-13, 114 mg).
[Example E-1 to 16] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-E-1. Rx'-O Table-E-1 Exp. Rx'O method RTime Mass E-1 cPenMeO E-2 cHexMeO Et Br E-1 E-2 E-3 Br E-1 A 5. 57 N. D E-4 2EtBuO Et Br E-1 E-5 cPenO Et Br E-1 A 5. 62 342 (M+) E-6 cHexO Et Br E-1 E-7 (R) 1 Et Br E-7 A 5. 60 N. D E-8 2 (4DMAPh) EtO Et Br E-7 E-9 2 (2FPh) EtO Et Br E-10 2 (3FPh) EtO Et Br E-7 E-11 2 (4CIPh) Et Br E-7 E-12 2 (PhO) EtO Et Br E-7 E-13 4CF3BnO Et Br E-13 A 5. 78 432 (M+) E-14 2MeBnO Et Br E-13 E-15 2CIBnO Et Br E-13 E-16 1 (4FPh) EtO Et Br E-7 G[Example F-1] Synthesis of 4- (3-bromo-4-methoxyphenyl) butyric acid (Intermediate 37) According to the procedure described in the synthesis method of Compound No. A-1 provided that the reaction was carried out under ice cooling for 30 minutes and for 20 hours at room temperature, 4- (4-methoxyphenyl) butyric acid (11.64 g, Ald) and NBS (11.21 g) were reacted and treated to obtain the title compound (Intermediate 37,16. 30 g).
Synthesis of methyl 4- (3-bromo-4-hydroxyphenyl) butyrate (Intermediate 38) According to the procedure described in the synthesis method of Intermediate 4, Intermediate 37 (12.51 g) and a 1 M solution of boron tribromide in methylene chloride (100 ml) were reacted and treated, and the obtained residue was reacted with thionyl chloride (8.4 ml) in methanol and treated according to the procedure described in the synthesis method of Intermediate 1 to obtain the title compound (Intermediate 38,10. 48 g).
Synthesis of methyl 4- (3-bromo-4-cyclopentylmethyloxyphenyl) butyrate (Compound No. F-1) According to the procedure described in the synthesis method of Compound No. A-6 provided that the purification was performed by column chromatography (Quad, hexane: isopropyl alcohol = 10 : 1), Intermediate 38 (2.72 g), PhsP (7.86 g), cyclopentane methanol (3.24 ml) and 40% DIAD (14.2 ml) were reacted and treated to obtain the title compound (Compound No. F-1, 3.33 g).
[Examples F-1 to F-4] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-F-l. zx Ru'-ou (CH2) nCOOY' Table-F-1 LCMS Exp. Rx'O Y'Zx'G n Syn I method RTime _ Mass F-1 cPenMeO Me H Br 3 F-1 F-2 cPenO Me H Br 3 F-3 cHexO Me 3 F-1 C F-4 (4FPh) EtO Me [Example G-1] Synthesis of methyl 3- [4-methoxy-3- (naphthalen-2-yl) phenyl] propionate (Intermediate 39) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by flash column chromatography (hexane : isopropyl ether = 8 : 1), Intermediate 20 (460 mg), 2-naphthaleneboronic acid (886 mg), 2 M aqueous sodium carbonate (1.6 ml) and (Ph3P) 4Pd (298 mg) were reacted and treated to obtain the title compound (Intermediate 39,580 mg).
Synthesis of 3- [4-methoxy-3- (naphthalen-2-yl) phenyl] propionic acid (Intermediate 40) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Intermediate 39 (773 mg) and 2 N aqueous sodium hydroxide (2.3 ml) were reacted and treated to obtain the title compound (Intermediate 40,674 mg).
Synthesis of methyl 3- [4-hydroxy-3- (naphthalen-2-yl) phenyl] propionate (Intermediate 41) According to the procedure described in the synthesis method of Intermediate 10, pyridine (5 ml), concentrated hydrochloric acid (5 ml), and Intermediate 40 (551 mg) were reacted and treated to obtain crude powder substance. This substance was reacted with thionyl chloride (282 g 1) in methanol and treated according to the procedure described in the synthesis method of Intermediate 1 to obtain the title compound (Intermediate 41,531 mg).
Synthesis of methyl 3- [4-cyclopentyloxy-3- (naphthalen-2-yl) phenyl] propionate (Compound No. G-1) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 15 hours, and the purification was performed by flash column chromatography (hexane: isopropyl ether = 6: 1), Intermediate 41 (100 mg), PhsP (262 mg), cyclopentanol (91 u 1, TCI) and 40% DIAD (473 u 1) were reacted and treated to obtain the title compound (Compound No. G-1, 120 mg).
[Example G-2] Synthesis of 3- [4-cyclopentyloxy-3- (naphthalen-2-yl) phenyl] propionic acid (Compound No. G-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 4 hours, Compound No. G-1 (115 mg), and 2 N aqueous sodium hydroxide (0.75 ml) were reacted and treated to obtain the title compound (Compound No. G-2,108 mg).
[Example G-3] Synthesis of methyl 3- [4-cyclopentyloxy-3- (lH-indol-5-yl) phenyl] propionate (Compound No. G-3) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 3 hours, and the purification was performed by flash column chromatography (hexane: ethyl acetate = 4: 1), Compound No. A-5 (833 mg), 5-indoleboronic acid (657 mg), 2 M aqueous sodium carbonate (2.4 ml) and (PhsP) 4Pd (233 mg) were reacted and treated to obtain the title compound (Compound No. G-3, 900 mg).
[Example G-4] Synthesis of 3- [4-cyclopentyloxy-3- (lH-indole-5-yl) phenyl] propionic acid (Compound No. G-4) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. G-3 (144 mg) and 2 N aqueous sodium hydroxide (420 u 1) were reacted and treated to obtain the title compound (Compound No. G-4, 127 mg).
[Example G-9] Synthesis of methyl 3- [4-benzyloxy-5- (I-methyl-lH-indazol-5-yl) phenyl] propionate (Compound No. G-9) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 6 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 4 : 1), Compound No. A-8 (349 mg), 1-methyl-lH-indazole-5-boronic acid (283 mg), 2 M aqueous sodium carbonate (0.9 ml) and (Ph3P) 4Pd (94.3 mg) were reacted and treated to obtain the title compound (Compound No. G-9, 370 mg).
[Example G-10] Synthesis of 3- [4-benzyloxy-5- (1-methyl-lH-indazol-5-yl) phenyl] propionic acid (Compound No. G-10) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 4 hours, Compound No. G-9 (80 mg) and 2 N aqueous sodium hydroxide (0.20 ml) were reacted and treated to obtain the title compound (Compound No. Go-10, 71 mg).
Synthesis of methyl 3- [4-hydroxy-5- (l-methyl-lH-indazol-5-yl) pheny propionate (Intermediate 42) A solution of Compound No. G-9 (314 mg) in a mixture of ethyl acetate (3 ml) and methanol (3 ml) was added with 10% palladium/carbon (12 mg), and stirred at room temperature for 16 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Intermediate 48,288 mg).
[Example G-23] Synthesis of methyl 3- (3-bromo-4-t-butyldimethylsilyloxyphenyl) propionate (Intermediate 43) According to the procedure described in the synthesis method of Intermediate 16 provided that the reaction was carried out for 16 hours, Intermediate 5 (5.18 g), imidazole (2.04 g) and t-butyldimethylsilyl chloride (4.52 g) were reacted and treated to obtain the title compound (Intermediate 43, 8. 42 g).
Synthesis of methyl 3- [4- (t-butyldimethylsilyloxy-3- (lH-indol-5- yl) phenyl) propionate (Intermediate 44) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that reaction was performed for 12.5 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 9 : 1), 5-indoleboronic acid (4.83 g), Intermediate 34 (7.46 g), 2 M aqueous sodium carbonate (18 ml) and (Ph3P) 4Pd (1.62 g) were reacted and treated to obtain the title compound (Intermediate 44,5. 04 g).
Synthesis of methyl 3- [4-hydroxy-3- (lH-indol-5-yl) phenyl propionate (Intermediate 45) According to the procedure described in the synthesis method of Intermediate 19 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 3: 1), Intermediate 35 (5.04 g), acetic acid (2.8 ml) and a 1 M solution of tetrabutylammonium fluoride in THF (49 ml, TCI) were reacted and treated to obtain the title compound (Intermediate 45,3. 13 g).
Synthesis of methyl 3- [3- (lH-indol-5-yl)-4- (4-methylphenylmethyloxy) phenyl]- propionate (Compound No. G-23) According to the procedure described in the synthesis method of Compound No. A-2 with the modifications that the reaction was carried out for 15 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 5 : 1), Intermediate 45 (80 mg), potassium carbonate (114 mg) and 4- methylbenzyl bromide (54 u 1, TCI) were reacted and treated to obtain the title compound (Compound No. G-23,104 mg).
[Example G-24] Synthesis of 3- [3- (lH-indol-5-yl)-4- (4-methylphenylmethyloxy) phenyl] propionic acid (Compound No. G-24) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. G-23 (99 mg) and 2 N aqueous sodium hydroxide (500, u 1) were reacted and treated to obtain the title compound (Compound No. G-24, 84 mg).
[Example G-106] Synthesis of N- [2- (t-butyldiphenylsilyloxy) ethyl] aniline (Intermediate 46) A solution of 2-anilinoethanol (5.82 g, TCI) in anhydrous DMF (50 ml) was added with imidazole (3.23 g, TCI), added dropwise with a solution of t-butyldiphenylsilyl chloride (12.48 g, TCI) in DMF (50 ml) under ice cooling, stirred for 30 minutes, then warmed to room temperature, and further stirred for 3.5 hours. The reaction mixture was added with water (100 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed successively with water and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 9: 1) to obtain the title compound (Intermediate 46,15. 61 g).
Synthesis of N-benzyl-N- [2- (t-butyldiphenylsilyloxy) ethyl] aniline (Intermediate 47) According to the procedure described in the synthesis method of Compound No. A-2 with the modifications that the reaction was carried out for 15 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 5 : 1), Intermediate 46 (15.60 g), potassium carbonate (8.91 g) and benzyl bromide (6.05 ml, TCI) were reacted and treated to obtain the title compound (Intermediate 47,19. 23 g).
Synthesis of 2- (N-benzyl-N-phenylamino) ethanol (Intermediate 48) According to the procedure described in the synthesis method of Intermediate 9 with the modifications that the reaction was carried out for 1 hour, and the purification was performed by flash column chromatography (hexane: ethyl acetate = 5: 1), Intermediate 47 (19.22 g) and a 1 M solution of tetrabutylammonium fluoride in THF (86 ml) were reacted and treated to obtain the title compound (Intermediate 48,9. 06 g).
Synthesis of methyl 3- {4- [2- (N-benzyl-N-phenylamino) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionate (Compound No. G-106) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 15 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 7: 1), Intermediate 41 (1.26 g), PhsP (1.34 g), Intermediate 48 (1.01 g) and DBAB (1. 18 g) instead of 40% DIAD were reacted and treated to obtain the title compound (Compound No. G-106,1. 39 g).
[Example G-107] Synthesis of methyl 3-{3-(naphthalen-2-yl)-4-[2-(N- phenylamino) ethyloxylphenyllpropionate (Compound No. G-107) A solution of Compound No. G-106 (1.39 g) in a mixture of THF (10 ml) and methanol (20 ml) was added with concentrated hydrochloric acid (75 u 1, WAKO) and 10% palladium/carbon (142 mg), and stirred at room temperature for 3 hours under hydrogen gas atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Compound No. G-107, 842 mg).
[Example G-108] Synthesis of 3-{3- (naphthalen-2-yl)-4- [2- (phenylamino) ethyloxy] phenyl} propionic acid (Compound No. G-108) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. G-107 (46 mg) and 2 N aqueous sodium hydroxide (0.25 ml) were reacted and treated to obtain the title compound (Compound No. Go-108, 41 mg).
[Examples G-1 to G-121] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-G-1 to Table-G-4. Zx Rx-O AR Table-G-1 Exp. RxO Y Zx AR Syn LCMS method Mass G-1 cPenMeO Me H 2-Nap G-1 C 388 (M+) G-2 cPenMeO H H 2-Nap G-2 C G-3 cPenMeO Me H 5-Ind G-3 G-4 cPenMeO H H 5-Ind G-4 C 363 (M+) G-5 cPenMeO Me H 1 Me-5-Ind G-6 cPenMeO H H lMe-5-lnd G-7 cPenMeO Me H 5-1 Hldz G-3 G-8 cPenMeO H H 5-1 HIdz G-4 G-9 BnO Me H G-10 BnO H H 1 G-11 cPenMeO Me H 1 G-3 G-12 cPenMeO H H 1 G-4 G-13 H H 2-Nap G-1, G-2 A G-14 2EtBuO H H 5-Ind G-4 G-15 4Me, cHexO H 2-Nap G-1. G-2 G-16 4Me, cHexO H H 5-Ind G-3. G-4 D 5. 46 378 (M++1) G-17 H H 2-Nap G-1, G-2 qp"o G-13 H H 5-Ind G-4 G-19 cHepO G-4 G-20 3PhPrO H H 2-Nap G-1, G-2 G-21 4PhBuO H H 5-Ind G-3, G-4 G-22 t< H 2-Nap G-1, G-2 D 5. 414 (M++1) 6 G-23 4MeBnO Me H 5-Ind G-23 G-24 4MeBnO H H 5-Ind G-25 2 (4MePh) EtO H H 2-Nap G-1, G-2 G-26 2 (4MePh) EtO H H 5-Ind G-1. G-2 G-27 4CIBnO H H 2-Nap G-23, G-24 G-28 4CF3BnO H H 5-Ind G-23, G-24 G-29 3F, 4 (OMe) BnO H H 2-Nap G-1. G-2 G-30 3F, 4 (OMe) BnO H H 5-Ind G-1, G-2 G-31 H H 2-Nap G-1, G-2 G-32 H H 5-Ind G-1, G-2 0 G-33 CFy H H 2-Nap G-1, G-2 G-34 H 5-Ind G-1, G-2 CF3 G-35 H H 2-Nap G-1, G-2 H H 5-Ind G-1, G-2 O YTable-G-2 G-37 11ndanO H H G-2 D G-38 2IndanO 2-Nap G-1, G-2 G-39 21ndanO H H 5-lnd G-40 H H 2-Nap G-1, G-2 G G-41 5, 6D (OMe)-2-IndanO H H 5-Ind G-1, G-2 C G-42 5F-2-IndanO 2-Nap G-l, G-2 G-43 5F-2-IndanO H H 5-Ind G-2 C G-44 WO G-1, G-2 G-45 cao H H 5-Ind G-2 A 5. 46 412 (M"+1) o G-46 H H 2-Nap G-1, G-2 o G-47 H H 5-1 HInd G-48 G-2 G-49 2 (2MePh) EtO H H 5-Ind G-1, G-2 G-50 2 (3FPh) EtO H H 2-Nap G-1, G-2 G-51 2 (2CIPh) H H 2-Nap G-1, G-2 G-52 2 (3CIPh) H H 5-Ind G-1, G-2 G-53 2 (2CF3Ph) EtO H H 5-Ind G-1. G-2 G-54 4 (CF3Ph) EtO H H 2-Nap G-1, G-2 G-55 2 (20MePh) EtO H H 2-Nap G-1, G-2 C G-56 2 (40MePh) EtO H H 5-Ind G-1, G-2 G-57 2 (1-NapEt) O H H 2-Nap G-1. G-2 G-58 2 (2-Nap) EtO H H 2-Nap G-1, G-2 G-59 2 (2-Nap) EtO H H 5-Ind G-1, G-2 C G-60 2 (4CIPh) H H 2-Nap G-1, G-2 G-61 Con H H 5-Ind G-1, G-2 D 5. 11 430 (M++1) G-62 Ct>) G-2 G-63 2 (PhS) EtO H H 2-Nap G-2 A G-64 2 (PhS) EtO H H 5-Ind G-1, G-2 G-65 3PhPrO H H 5-Ind G-1, G-2 G-66 2CIBnO H H 2-Nap G-1. G-2 G-67 2BrBnO H H 5-Ind G-1, G-2 C G-68 3, 5DMeBnO H H 5-Ind G-1, G-2 G-69 4tBuBnO H H 2-Nap G-1, G-2 G-70 2CF3BnO H H 2-Nap G-1, G-2 G-71 4CF3BnO H H 5-Ind G-1, G-2 G-72 4nBuBnO H H 5-Ind G-73 3, 5DCIBnO H H 2-Nap G-1, G-2 G-74 2, H H 5-Ind G-1, G-2 G-75 2PhBnO H H 2-Nap G-1, G-2 G-76 4PhBnO H H 5-Ind G-1, G-2 A 5-Ind G-1,Table-G-3 i G-77 p'NN 2-Nap G-1. G-2 m G-78 fL<N H H 5-Ind G-2 0 1 G-79 H H 2-Nap G-1, G-2 IN' G-80 H H 5-Ind G-1, G-2 nul' G-81 t H H 2-Nap G-1, G-2 C 386 (M++1) G-82 '\o H H 5-Ind G-1, G-2 _o G-83 o H H 2-Nap G-1, G-2 tJO G-84 at G-2 o. G-B6 H H 2-Nap G-1, G-2 G-86 G-2 0 G-67 H H 2-Nap G-1, G-2 0 G-88 9 H 5-Ind G-1, G-2 0 G-89 Q G-90 9 H H 5-Ind G-1, G-2 G-91 H 2-Nap G-1, G-2 G-91 I'O H G-92 G-2 G-93 F3 H H 2-Nap G-1, G-2 C, 10, ll'0 G-94 . H H 2-Nap G-1, G-2 C 384 (M++1) Lo G-95 H H 5-Ind G-1, G-2 G-96 H H 2-Nap G-1, G-2 G-97 H H 5-Ind G-1, G-2 N H NTable-G-4 G-96 H 2-Nap G-1, G-2 0 H G-2 G-100 H H 2-Nap G-1, G-2 <- G-101 C H H 5-Ind G-1, G-2 C 423 (M++1) G-1, G-2 G-102 rio H H 2-Nap G-103 4 H H 5-Ind G-1, G-2 G-104 ° G-105 ° H H 5-Ind G-1, G-2 G-106 2 (Ph, BnN) EtO Me G-107 2 (PhNH) EtO Me G-107 G-108 2 (PhNH) EtO H H 2-Nap G-108 C G-109 2 (PhNH) EtO Me H 5-Ind G-107 G-110 2 (PhNH) EtO H H 5-Ind G-108 G-111 2 (PhNH) EtO Me H 1Me-5-Ind G-112 2 (PhNH) EtO H H 1 Me-5-Ind G-108 C G-113 Me H 5-1 G-114 2 (PhNH) EtO H H 5-1 Hldz G-108 G-115 2 (PhNH) EtO Me H 1Me-5-lHIdz A 4. 76 430 (M++1) G-116 2 (PhNH) EtO H H 1 G-117 H H 1 G-2 C G-118 H H G-2 C G-119 H H G-4 A 4. 10 373 (M++1) G-120 H H 1 G-4 A 4. 46 G-121 H H 1 G-4 A 4. 12 403 (M++l) t H [Examples H-1 to H-32] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table-H-1 and Table-H-2. Zx Rx-O AR Table-H-1 Exp. RxO Y Zx AR Syn method RTime Mass N--N H-1 Me H 2-Nap G-1 0 r4=N H-2 H 2-Nap G-2 N=N N=N H-3 N Me H 5-Ind G-1 C 375 (M \ H-4 cr H H 5-Ind G-2 NZN H-5 Cr, Me H G-1 0 N=N H-6 H NON H-7 Me H 5-1 G-1 0 H-8 ' H H 5-1 Hldz G-2 0 N=N H-9 Me H 1 G-1 N= H-10 G-2 C 454 (M++1) H-11 H 2-Nap G-1, G-2 H-12 H 1 Me-5-Ind G-1 G-2 G 452 (M++1) rop H-13 N H H 2-Nap G-1, G-2 0 H-14 » H 1 Me-5-Ind G-1, G-2 _ H-15 N. -b H H 2-Nap G-1, G-2 464 (M++1) H-16 O$b H 1 Me-5-Ind G-1, G-2 H-17 H H 2-Nap G-1, G-2 C 450 (M++1) H-1 8 H 1 Me-5-Ind G-1, G-2 LCMSTable-H-2 H-19 A H 2-Nap G-1, G-2 H-20 ° o H-21 H 2-Nap G-1, G-2 0 H-22 r-N H 1 G-2 C 471 (M++1) 0--Y H-23 0-mi H H 2-Nap G-1, G-2 H-24 H H 1 G-2 H-25 H H 2-Nap G-1, G-2 H-26 0 H H 1Me-5-Ind G-2 H-27 Xb H 2-Nap G-1, G-2 H-28 H H 1 G-2 C 460 (M++1) H-29 H H 2-Nap G-1, G-2 H-30 fit-\ H 1 Me-5-Ind G-1, G-2 H-31 H G-2 C 452 (M++l) H-32 H H H Me-5-Ind G-2 [Example J-1] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3-fluoro-5- (lH-indol-5- yl) phenyllpropionate (Compound No. J-1) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 10: 1), Compound No. A-21 (154 mg), 5-indoleboronic acid (100 mg), 2 M aqueous sodium carbonate (1.5 ml) and (Ph3P) 4Pd (50 mg) were reacted and treated to obtain the title compound (Compound No. J-1, 125 mg).
[Example J-2] Synthesis of 3- [4-cyclopentylmethyloxy-3-fluoro-5- (lH-indol-5-yl) phenyl] propionic acid (Compound No. J-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. J-1 (124 mg) and 2 N aqueous sodium hydroxide (630 1) were reacted and treated to obtain the title compound (Compound No. J-2, 97 mg).
[Example J-3] Synthesis of methyl 3- [3-chloro-4-cyclopentylmethyloxy-5- (lH-indol-5- yl) phenyl] propionate (Compound No. J-3) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 10: 1), Compound No. A-20 (151 mg), 5-indoleboronic acid (97 mg), 2 M aqueous sodium carbonate (1.5 ml) and (Ph3P) 4Pd (46 mg) were reacted and treated to obtain the title compound (Compound No. J-3, 160 mg).
[Example J-4] Synthesis of 3- [3-chloro-4-cyclopentylmethyloxy-5- (lH-indol-5-yl) phenyl] propionic acid (Compound No. J-4) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. J-3 (135 mg) and 2 N aqueous sodium hydroxide (660 u 1) were reacted and treated to obtain the title compound (Compound No. J-4, 97 mg).
[Examples J-1 to J-92] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table'J'l to Table-J-3 Zx Rx-O AR Table-J-1 .."_..- Exp. RxO Y Zx AR Syn method mr mn J-1 cPenMeO Me F 5-lnd J-2 cPenMeO H F 5-Ind J-2 J-3 cPenMeO Me J-4 cPenMeO H CI 5-Ind J-5 cPenMeO Me F 2-Nap J-1 J-6 J-6 J-7 cPenMeO Me F 1 J-1 J-8 cPenMeO H F J-9 cPenMeO Me-F J-10 cPenMeO H F 5-1 J-2 J-11 cPenMeO Me F 1 J-12 cPenMeO H F'i J-2 C J-13 2EtBuO H F 2-Nap G-1, G-2 J-14 2EtBuO H F 5-tnd G-2 J-15 4Me, cHexO H F 2-Nap G-1, G-2 J-16 4Me. cHexO H F 1Me-5-Ind G-2 Lo J-17 H F 2-Nap G-1, G-2 Wo - Jo J-18 H F 1 G-2 C 452 I J-19 H F 2-Nap G-1, G-2 J-20 3PhPrO H F lMe-5-Ind G-2 J-21 4PhBuO H F 2-Nap G-1, G-2 J-22 G-2 J-23 1 (4MePh) EtO H F 2-Nap J-24 4CIBnO H F 1Me-5-Ind G-2 J-25 4CF3BnO H F 2-Nap G-1, G-2 J-26 3F, 4 (OMe) BnO H F 1Me-5-Ind G-2 J-27 H F 2-Nap G-1, G-2 C 429 (M++1) J-28 @ H F 1Me-5-Ind G-2 0 J-29 Cv H F 1Me-5-Ind G-2 0 J-30 H F 2-Nap G-1, G-2 F J-31 C/~ G-2 X °-YTable-J-2 J-32 1-IndanO H F 2-Nap G-1, G-2 J-33 2-IndaneO H F 1Me-5-Ind G-2 J-34 2-IndaneO H F 2-Nap G-1, G-2 J-35 50Me-2-IndanO H F 1Me-5-Ind G-2 J-36 5, OD (OMe)-2-lNdanO F 2-Nap G-1, G-2 J-37 5F-2-IndanO H F 2-Nap G-1, G-2 J-38 5F-2-IndanO H F 1Me-5-Ind G-2 J-39 Qdo H F 2-Nap G-1, G-2 G _ J-40 0 H F 1 G-2 ' J-41 2 (3MePh) Et0 2-Nap G-1, G-2 J-42 2 (4MePh) EtO H F 1Me-5-Ind G-2 J-43 2 (2CIPh) H F 1 J-44 2 (3CIPh) H F 2-Nap G-1, G-2 J-45 2 (2CF3Ph) H F 2-Nap G-1, G-2 J-46 2 (20MePh) EtO H F 1 J-47 2 (40MePh) EtO H F 2-Nap G-1. G-2 J-48 2 (2-Nap) EtO H F lMe-5-Ind G-2 J-49 Q° H F 2-Nap G-1, G-2 C 458 (M++l) Xco J-50 0 H F 1 G-2 J-51 2 (PhS) EtO H F 1Me-5-Ind J-52 3PhPrO H F 2-Nap G-1, G-2 J-53 2CIBnO H F 1Me-5-Ind G-2 J-54 2BrBnO H F 2-Nap G-1, G-2 J-55 3, 5DMeBnO H F 2-Nap G-1, G-2 v J-56 4tBuBnO H F 1 G-2 C J-57 2CF3BnO H F 1Me-5-Ind G-2 J-58 4CF3BnO H F 2-Nap G-1, G-2 J-59 4nBuOBnO H F 2-Nap G-1. J-60 3, H F 1Me-5-Ind G-2 J-61 2, 3DCIBnO H F 2-Nap G-1, G-2 J-62 2-NapMeO H F 2-Nap G-1, G-2 C J-63 1-NapMeO H F 1 J-64 2PhBnO H F 1Me-5-Ind G-2 J-65 4PhBnO H F I G-2 J-66 50Me-2-Indano H F 2-Nap G-1, J-67 50Me-2-IndanO H F 1 G-2 J-68 5, 6D (OMe)-2-IndanOH F 2-Nap G-1, G-2 J-69 5, 6D (OMe)-2-lndanO F 1 G-2 J-70 5F-2-IndanO F 2-Nap J-71 G-1,Table-J-3 J-72 ; H 1 G-2 C)'\ N J-73 H F 2-Nap G-2 C 481 J-74 G-2 i J-75 Chxo J-76 4N5o H F 1 G-2 0 J-77/CGC H F 1Me-5-lHldz G-2 C 410 o. J-78 H F 1Me-5-Ind zoo 0-\ J-79 G-2 . J-80 H F N_, J-81 I G-2 J-82 F3C G-2 J-83 1 u,-o I J-84 G-2 1q"0 J-85 H F G-2 C 419 (M++l) J-86 G-2 J-asz H F 2-Nap G-1, G-2 J-88 N,, G-2 J-89 li-S r-S H F 2-Nap G-1, G-2 C 436 (M++1) J-90 G-2 S J-91 \o 2-Nap G-l, G-2 ---------------------------------------------- J-92 H G-2 [Example K-11] Synthesis of methyl 3- [3-bromo-4-cyclopentylmethyloxy-5- (naphthalen-2- yl)phenyl]propionate (Compound No. K-11) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 15 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 9: 1), Compound No. B-117 (306 mg), 2-naphthaleneboronic acid (163 mg), 2 M aqueous sodium carbonate (689 A l) and (Ph3P) 4Pd (74.2 mg) were reacted and treated to obtain the title compound (Compound No. K-11, 261 mg).
Synthesis of 3- [3-bromo-4-cyclopentylmethyloxy-5- (lH-indol-5-yl) phenyl] propionic acid (Compound No. K-12) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. K-11 (131 mg) and 2 N aqueous sodium hydroxide (400, u 1) were reacted and treated to obtain the title compound (Compound No. K-12, 109 mg).
[Example K-13] Synthesis of methyl 3- [3-bromo-4-cyclopentylmethyloxy-5- (lH-indol-5- yl) phenyl] propionate (Compound No. K-13) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 5: 1), Compound No. B-117 (102 mg), 5-indoleboronic acid (97 mg), 2 M aqueous sodium carbonate (1.5 ml) and (Ph3P) 4Pd (46 mg) were reacted and treated to obtain the title compound (Compound No. K-13, 85 mg).
[Example K-14] Synthesis of 3- [3-bromo-4-cyclopentylmethyloxy-5- (lH-indol-5-yl) phenyl] propionic acid (Compound No. K-14) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. K-13 (85 mg) and 2 N aqueous sodium hydroxide (200 u 1) were reacted and treated to obtain the title compound (Compound No. K-14,79 mg).
[Example K-17] Synthesis of methyl 3- [3-bromo-4-cyclopentyloxy-5- (1-methyl-lH-indazol-5- yl) phenyl] propionate (Compound No. K-17) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 14 hours at 80°C, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 4 : 1), Compound No. B-118 (306 mg), 1-methyl-lH-indazole- 5-boronic acid (175 mg), 2 M aqueous sodium carbonate (0.68 ml) and (Ph3P) 4Pd (70. 1 mg) were reacted and treated to obtain the title compound (Compound No. K- 17,148 mg).
[Examples K-1 to K-40] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-K-l and Table-K-2. Zx -K-1 able A _ Exp. RxO Y Zx AR Syn LCMS method Mass K-1 ONT Me F 2-Nap G-1 K-2 ON>o H F 2-Nap G-2 FN. K-3 AN Me F 5-Ind G-1 0 K-4 C H F 5-Ind G-2 C 457 (M-'*+l) _ K-5 Crß G-1 0 1 1 1 K-6 G-2 C 471 (M++l) N-N. K-7 > Me F 5-1 G-1 . K-8 Q""o F 5-1 G-2 1'IV K-9 aN N K-10 G-2 K-11 K-12 cPenMeO H Br 2-Nap K-12 K-13 cPenMeO Me Br 2-Nap K-13 K-14 cPenMeO H Br 5-Ind Int50, K-15 cPenO H Br 2-Nap K-11 K-16 cPenO H Br 1 K-17 cPenO Me Br 1 K-18 cPenO H Br 1 A 4. 78 443 (M+) K-19 H F 2-Nap G-1, G-2 K-20 H G-1, G-2 K-21 H F 2-Nap G-1, G-2 o K-22 » F 1 G-2 o K-23 -NN G-1, G-2 (t-0 K-24 O#NSO H F 1Me-5-Ind G-1, G-2 C 485 (M++1) 0 K-25 eok H F 2-Nap G-1, G-2 vo K-26 owN H F 1 G-1, G-2 Rx-o,Table-K-2 o K-27 N H F 2-Nap G-1, G-2 _ K-28 H H F 1Me-5-Ind G-2 s K-29 G-2 01-Y K-30 H H F 1Me-5-Ind G-2 0-i I F G-2 C 486 (M++1) 0 K-32 @ G-2 K-33 ag H F 2-Nap G-1, G-2 K-34 0-0 F 1 G-2 C 511 (M++1) K-35 H F 2-Nap G-1, G-2 K-36 X H F 1Me-5-Ind G-2 K-37 G-2 4f, K-38'''-° G-2 SJ-S K-39 0 G-2 K-40-0 G-2 [Example L-1] Synthesis of 3- [4-cyclop entyloxy-3-methyl-5- (naphthalen-2-yl) phenyl] propionic acid (Compound No. L-1) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 6 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 20: 1), Compound A-24 (63 mg), 2-naphthaleneboronic acid (67 mg), 2 M aqueous sodium carbonate (130, u 1) and (Ph3P) 4Pd (18 mg) were reacted and treated. The obtained substance was reacted with 2 N aqueous sodium hydroxide (200 u 1) and treated according to the procedure described in the synthesis method of Intermediate 9 to obtain the title compound (Compound No. L-1, 25 mg).
[Example L-2] Synthesis of methyl 3- [4-cyclopentyloxy-3-methyl-5- (1-methyl-lH-indazol-5- yl) phenyl] propionate (Compound No. L-2) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 12 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 4: 1), Compound No. K-17 (115 mg), methylboronic acid (66 mg, Ald), 2 M aqueous sodium carbonate (0.40 ml) and (Ph3P) 4Pd (39.4 mg) were reacted and treated to obtain the title compound (Intermediate 52,84 mg).
[Example L-3] Synthesis of 3- [4-cyclopentyloxy-3-methyl-5- (1-methyl-lH-indazol-5- yl) phenyl] propionic acid (Compound No. L-3) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1.5 hours, Compound No. L-2 (82 mg) and 2 N aqueous sodium hydroxide (0.26 ml) were reacted and treated to obtain the title compound (Compound No. L-3, 62 mg).
[Examples L-1 to L-95] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-L-1 to Table-L-3. Rx Rx-O AR Table-L-1 Exp. RxO Y Zx AR Syn. LCMS method r L-1 cPenO H Me 2-Nap L-1 A 5. 65 375 (M++l) L-2 cPenO Me Me 1 L-3 cPenO H Me 1 L-3 A 4. 50 379 (M++1) L-4 2EtBuO Me Me 2-Nap L-2 L-5 2EtBuO H Me 2-Nap L-3 C L-6 2EtBuO H Me 6-OMe-2-Nap L-2, L-3 L-7 2EtBuO Me Me 5-Ind L-2 L-8 2EtBuO H Me 5-Ind L-3 L-9 2EtBuO Me Me L-10 H Me 1Me-5-Ind L-11 Me Me 5-1 Hldz L-2 L-12 H Me 5-1 HIdz L-3 L-13 Me Me 1 L-14 H Me lMe-5-lHIdz L-3 C L-15 Me Me 5-Bzt L-2 L-1 H Me 5-Bzt L-3 L-17 Me Me 5-2ABzt L-2 L-18 H Me 5-2ABzt L-3 L-19 Me Me 2Me-5-Bzt L-2 L-20 2EtBuO H Me 2Me-5-Bzt L-3 L-21 4Me, cHexO H Me 1Me-5-Ind G-2 , L-22 Me 2-Nap G-1, G-2 L-23 cHepO Me 2-Nap G-1, G-2 L-24 cHepO H Me 1Me-5-Ind G-2 C L-25 3PhPrO H Me 2-Nap G-1, G-2 L-26 4PhBuO H Me G-2 L-27 Me 2-Nap G-1, G-2 L-28 1 (4MePh) EtO H Me 1 G-2 C L-29 4CIBnO H Me 2-Nap G-1, G-2 L-30 4CF3BnO H Me 1Me-5-Ind G-2 L-31 3F, 4 (OMe) BnO H Me 2-Nap G-1, G-2 L-32 ( G-2 / L-33 H Me 2-Nap G-1, G-2 0 t34 H Me 2-Nap G-1, G-2 . L-35 H Me 1Me-5-Ind G-2 CF3 ATable-L-2 L-36 CH G-2 L-37 H Me 1Me-5-Ind G-1, G-2 L-38 L-39 2-IndanO H Me G-2 C L-40 2-IndanO H Me 1Me-5-Ind G-2 L-41 50Me-2-IndanO H Me 1 L-42 5, 6D (OMe)-2-lndanO H Me 2-Nap G-1, G-2 L-43 5F-2-IndaneO H Me 2-Nap G-1, G-2 L-44 5F-2-IndaneO H Me 1Me-5-Ind G-2 L-45 calo H Me 1Me-5-Ind G-1, G-2 L-46 H Me 2-Nap G-1, G-2 L-47 2 (3MePh) EtO H Me 2-Nap G-1, G-2 L-48 2 (3FPh) EtO H Me lMe-5-lnd G-2 C L-49 2 (2CIPh) H Me 1Me-5-Ind G-2 L-50 2 (4CF3Ph) EtO H Me 1 G-2 L-51 2 (20MePh) EtO H Me 2-Nap G-1, G-2 C L-52 2 (40MePh) EtO H Me 1 G-2 L-53 2 H Me 2-Nap L-54 2 (2-Nap) EtO H Me 1 G-2 L-55 0""° H Me G-2 L-56 CEOF H Me 1 G-1, G-2 C 459 (M++1) L-57 2 (PhS) EtO L-58 3PhPrO H Me 1Me-5-Ind G-1, G-2 L-59 2CIBnO H Me 2-Nap G-1, G-2 L-60 2BrBnO H Me 1Me-5-Ind G-1, G-2 L-61 3, 5DMeBnO H Me 2-Nap G-1, G-2 L-62 4tBuBnO H Me 2-Nap G-1, G-2 L-63 2CF3BnO H Me 2-Nap G-1, G-2 L-64 4tBuBnO H Me 1Me-5-Ind G-1, G-2 L-65 4nBuBnO H Me 2-Nap G-1, G-2 C L-66 3, 5DCIBnO H Me 2-Nap G-1. G-2 L-67 2, 3DCIBnO H Me 1Me-5-Ind G-1, G-2 L-68 2-NapMeO H Me 1Me-5-Ind G-2 L-69 1-NapMeO H Me 2-Nap G-1, G-2 L-70 2PhBnO H Me 1Me-5-Ind G-1, G-2 L-71 4PhBnO H Me 2-Nap G-1, G-2 C L-72 50Me-2-IndanO H Me 1Me-5-Ind G-1, G-2 L-73 5F-2-IndaneO H H Me 1 Me-5-Ind G-1,Table-L-3 L-74 N H Me 2-Nap G-1, G-2 C 401 (M++1) N L-75 H G-2 L-76 H Me 2-Nap G-1, G-2 N L-77 H Me L-78 H Me 2-Nap G-1, G-2 (cl) L-79 Me 1 G-2 0 L-80 @_|g Me 2-Nap G-1, G-2 _. o L-81 9 H Me 1 G-2 o> H Me 2-Nap G-1, G-2 C 412 L-82'O L-83 N"H G-2 0, :) l' L-84 F3C, G-2 L-84 ( :) Io L-85 L-86 bX G-2 L-67 H Me 1 G-2 L-88 Me 2-Nap G-1, G-2 t--0 L-89 N,, Me 1 G-2 C 415 (M++1) L-90 0 Me 2-Nap G-1, G-2 L-91 -0 H Me 1 G-2 L-92 t Me 2-Nap G-1, G-2 ,'S L-93 Nap H G-2 C 435 (M++1) \S L-94 1-' G-2 L-95 H Me G-2 [Examples M-1 to M-32] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table-M-1 and Table-M-2. Zx RO- {YO-Y Table-M-1 Exp Exp. RxO Y Zx AR Syn method M-1 Me Me 2-Nap G-1 C 478 (M++1) o M-2 H Me 2-Nap G-2 C 464 (M++1) N=N M-3 Me Me 5-Ind G-1 N=N M-4 H Me 5-Ind G-2 N-N M-5 Me Me G-1 I I M-6 ONNW G-2 C 467 (M++1) Nt. M-7 CrtP, Me Me 5-1 G-1 N-N M-8 ONNm H Me 5-1 G-2 N2. M-9 aNW Me Me 1 G-1 Q N"N M-10 H Me G-2 Q M-11'o C 463 (M++1) M-'12 G-1, G-2 M-13 Me 2-Nap G-1, G-2 0 M-14 O ''N, H Me 1Me-5-Ind G-2 C 465 (M++1 0 M-15 H Me 2-Nap G-1, G-2 N< M-16 6 H Me 1 Me-5-Ind G-2 v M-1 H Me 2-Nap G-1, G-2 C 464 (M++1) C) M-18 < H Me G-1, G-2 0 M-19 9 H Me 2-Nap G-1, G-2 _ M-20 tof H Me 1Me-5-Ind G-2 0 M-21 N H Me 2-Nap G-1, G-2 ATable-M-2 o-, M-22 C6-, C) M-23 H Me 2-Nap G-1, G-2 N H Me 1 G-2 C 0 M-25 H Me 2-Nap G-1, G-2 M-26 e M-26 M-27 Me 2-Nap G-1, G-2 M-28 H G-2 M-29 H Me 2-Nap G-1, G-2 M-30 H Me G-2 C 472 (M++1) M-31 H Me 2-Nap G-1, G-2 0 M-32 QfN~O H G-2 [Example N-1] Synthesis of methyl 3- {4- [2- (N-acetyl-N-phenylamino) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionate (Compound No. N-1) A solution of Compound No. G-107 (32 mg) in methylene chloride (1 ml) was added with pyridine (24 u 1, TCI) and acetyl chloride (21 u 1, TCI), and stirred for 17 hours. The reaction mixture was added with water (3 ml), and extracted with methylene chloride (10 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 2 : 1) to obtain the title compound (Compound No. N-1, 28. 1 mg).
[Example N-2] Synthesis of 3-{4- [2- (N-acetyl-N-phenylamino) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionic acid (Compound No. N-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. N-1 (28 mg) and 2 N aqueous sodium hydroxide (0.25 ml) were reacted and treated to obtain the title compound (Compound No. N-2, 22 mg).
[Example N-29] Synthesis of methyl 3- {4- [2- (N-methoxycarbonyl-N-phenylamino) ethyloxy]-3- (naphthalen-2-yl) phenyl} propionate (Compound No. N-29) According to the procedure described in the synthesis method of Compound No. N-1, Compound No. G-107 (32 mg), pyridine (23 u 1) and methyl chloroformate (23 u 1, TCI) were reacted and treated to obtain the title compound (Compound No.
N-29,17. 3 mg).
[Example N-30] Synthesis of 3- {4- [2- (N-methoxycarbonyl-N-phenylamino) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionic acid (Compound No. N-30) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. N-29 (17 mg) and 2 N aqueous sodium hydroxide (0.25 ml) were reacted and treated to obtain the title compound (Compound No. N-30, 10.1 mg).
[Example N-48] Synthesis of methyl 3- {4- [2- (N-methylsulfonyl-N-phenylamino) ethyloxy]-3- (naphthalen-2-yl) phenyl} propionate (Compound No. N-48) According to the procedure described in the synthesis method of Compound No. N-1, Compound No. G-107 (32 mg), pyridine (24 u 1) and methanesulfonyl chloride (23 u 1) were reacted and treated to obtain the title compound (Compound No. N-48,32. 3 mg).
[Example N-49] Synthesis of 3- {4- [2- (N-methylsulfonyl-N-phenylamino) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionic acid (Compound No. N-49) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. N-48 (32 mg) and 2 N aqueous sodium hydroxide (0.25 ml) were reacted and treated to obtain the title compound (Compound No. N-49, 17 mg).
[Example N-55] Synthesis of methyl 3- {4- [2- (3-ethyl-1-phenylureido) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionate (Compound No. N-55) According to the procedure described in the synthesis method of Compound No. N-1 provided that the reaction was carried out for 41 hours, Compound No. G- 107 (32 mg), pyridine (24 u 1) and ethyl isocyanate (24 u 1, Nakarai Tecs) were reacted and treated to obtain the title compound (Compound No. N-55, 31.2 mg).
[Example N-56] Synthesis of 3- {4- [2- (3-ethyl-1-phenylureido) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionic acid (Compound No. N-56) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. N-55 (31 mg) and 2 N aqueous sodium hydroxide (0.25 ml) were reacted and treated to obtain the title compound (Compound No. N-56,15 mg).
[Example N-64] Synthesis of methyl 3-{4-[2-(3-ethyl-1-phenylthioureido) ethyloxy]-3-(naphthalen-2- yl) phenyl} propionate (Compound No. N-64) According to the procedure described in the synthesis method of Compound No. N-1 provided that the reaction was carried out for 41 hours, Compound No. G- 107 (32 mg), pyridine (24 u 1) and ethyl isothiocyanate (21 1, Nakarai Tecs) were reacted and treated to obtain the title compound (Compound No. N-64, 27.4 mg).
[Example N-65] Synthesis of 3- {4- [2- (3-ethyl-1-phenylthioureido) ethyloxy]-3- (naphthalen-2- yl) phenyl} propionic acid (Compound No. N-65) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. N-64 (27 mg) and 2 N aqueous sodium hydroxide (0.25 ml) were reacted and treated to obtain the title compound (Compound No. N-65, 8.9 mg).
[Examples N-1 to N-74] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-1 and Table-N-2. Zx 03 w N5 O f O Table-N-1 m Exp. A'Re Y Zx AR Syn Method RTime Mass N-1 COMe Me H 2-Nap N-1 N-2 COMe H H 2-Nap N-2 N-3 COMe Me H N-1 N-4 COMe H H 5-Ind N-2 C N-5 COMe Me H 1 N-1 N-6 COMe H H 1 N-2 N-7 COMe Me H 5-1 N-8 COMe H H 5-1HIdz N-2 N-9 COMe Me H 1 N-1 N-10 H H 1 N-2 N-11 H H 2-Nap N-1, N-2 C N-12 H H 1 N-2 N-13 H H N-2 N-14 H H 1 N-2 N-15 COiPr H H 2-Nap N-1, N-2 C N-16 COiPr H H 1Me-5-Ind N-2 N-17 (Et) nBu H H 2-Nap N-1, N'2 N-18 COCH (Et) nBu H H N-2 N-19 H H 2-Nap N-1, N-2 N-20 COCH2OMe H H 1Me-5-Ind N-2 N-21 COCH=CHMe H H 2-Nap N-1, N-2 N-22 COCH=CHMe H H 1 N-1, N-2 C N-23 COiBu H H 2-Nap N-1, N-2 N-24 COiBu H H 1Me-5-Ind N-2 N-25 COcPr H H 2-Nap N-1. N-2 N-26 COcPr H H 1Me-5-Ind N-2 C N-27 CO (CH2) H H 2-Nap N-1, N-2 N-28 CO H H 1Me-5-Ind N-1, N-2 N-29 COOMe Me H 2-Nap N-29 N-30 COOMe H H 2-Nap N-30 N-31 COOMe H H 1 N-30 N-32 COOPh H H 2-Nap N-29, N-30 C N-33 COOPh H H 1 N-30 N-34 CONMe2 H H 2-Nap N-29, N-30 C N-35 CONMe2 H H 1Me-5-Ind N-30 N-36 COOiBu H N-30 N-37 COOiBu H H iMe-5-lnd N-30 N-38 C (O) SMe H H 2-Nap N-29, N-30 N-39 C (O) SMe H H 1 N-30 N-40 *tNi H H 2-Nap N-29, N-30 . N-41 tNv N-30 C 528 (M++1) ZXTable-N-2 N-42 H H 2-Nap Int53, N-29 4--F N-43 SN3 H 1 Me-5-Ind Int53, N-29 N-44 COO (CH2) 2OMe H H 2-Nap Int53 N-29 N-45 COO (CH2) 2OMe H H 1 N-46 O*ND H H 2-Nap Int53, N-29 N-47 H 1 Me-5-Ind Int53, N-29 N-48 SO2Me Me H 2-Nap N-48 N-49 SO2Me H H 2-Nap N-49 N-50 SO2Me H H 1 N-49 C N-51 SO2Ph H H 2-Nap N-52 SO2Ph H H 1 N-49 N-53 SO2NMe2 H H 2-Nap N-48, N-49 C N-54 SO2NMe2 H H 1 N-49 N-55 CONHEt Me H 2-Nap N-55 N-56 CONHEt H H 2-Nap N-56 C N-57 CONHEt H H 1 N-56 N-58 CONHPh H H 2-Nap N-55, N-56 N-59 CONHPh H H 1 N-56 N-60 CONHcHex H H 2-Nap N-55, N-56 N-61 CONHcHex H H 1 N-56 C N-62 CONHBn H H 2-Nap N-55, N-56 N-63 CONHBn H H 1 N-56 N-64 CSNHMe Me H 2-Nap N-64 N-65 CSNHMe H H N-66 CSNHMe H H 1 N-65 N-67 CSNHPh H H 2-Nap N-64, N-65 N-68 CSNHPh H H 1 N-65 N-69 CSNH (3-Py) H H 2-Nap N-64, N-65 C N-70 CSNH (3-Py) H H 1 N-65 N-71 CSNHiPr H H 2-Nap N-64, N-65 N-72 CSNHiPr H H 1 N-65 C N-73 CSNHBn H H N-74 CSNHBn H H 1 N-65 [Example P-1] Synthesis of ethyl 3- [2-cyclopentylmethyloxy-3- (naphthalen-2-yl) pyridin-5- yl] propionate (Compound No. P-1) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 14 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 5: 1), 2-naphthaleneboronic acid (119 mg), Compound No. E-1 (83 mg), 2 M aqueous sodium carbonate (0.3 ml) and (PhsP) 4Pd (38.1 mg) were reacted and treated to obtain the title compound (Compound No. P-1, 76 mg).
[Example P-2] Synthesis of 3- [2-cyclopentylmethyloxy-3- (naphthalen-2-yl) pyridin-5-yllpropionic acid (Compound No. P-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. P-1 (47.8 mg) and 2 N aqueous sodium hydroxide (0.2 ml) were reacted and treated to obtain the title compound (Compound No. P-2, 20 mg).
[Example P-36] Synthesis of ethyl 3-{3-(naphthalen-2-yl)-2- [(R)-l-phenylethyloxy] pyridin-5- yl} propionate (Compound No. P-36) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 6: 1), 2-naphthaleneboronic acid (44 mg), Compound No. E-7 (73.3 mg), 2 M aqueous sodium carbonate (120, u 1) and (Ph3P) 4Pd (21.3 mg) were reacted and treated to obtain the title compound (Compound No. P-36, 44 mg).
[Example P-37] Synthesis of 3- {3- (naphthalen-2-yl)-2- [(R)-1-phenylethyloxy] pyridin-5-yl} propionic acid (Compound No. P-37) According to the procedure described in the synthesis method of Intermediate 9, Compound No. P-36 (41.2 mg) and 2 N aqueous sodium hydroxide (0.1 ml) were reacted and treated to obtain the title compound (Compound No. P-37, 38 mg).
[Example P-42] Synthesis of ethyl 3- {3- (naphthalen-2-yl)-2- [4- (trifluoromethyl) phenylmethyloxy] pyridin-5-yl} propionate (Compound No. P-42) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 6 : 1), 2-naphthaleneboronic acid (37.4 mg), Compound No. E-13 (42.4 mg), 2 M aqueous sodium carbonate (90 u 1) and (Ph3P) 4Pd (21.4 mg) were reacted and treated to obtain the title compound (Compound No. P-42,30. 4 mg).
[Example P-43] Synthesis of 3- {3- (naphthalen-2-yl) -2- [4- (trifluoromethyl) phenylmethyloxy] pyridin- 5-yl} propionic acid (Compound No. P-43) According to the procedure described in the synthesis method of Intermediate 9, Compound No. P-42 (29.5 mg) and 2 N aqueous sodium hydroxide (0.15 ml) were reacted and treated to obtain the title compound (Compound No. P- 43,24. 1 mg).
[Examples P-1 to P-50] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-P-1 and Table-P-2. Rx AR Table-P-1 ,..,. Exp. RxO Y AR Syn method irs P-1 cPenMeO Et 2-Nap P-1 P-2 cPenMeO H 2-Nap P-2 A 5. 60 376 (M++1) P-3 cPenMeO Et 5-Ind P-1 A 5. 37 393 (M++1) P-4 cPenMeO H 5-Ind P-2 P-5 cPenMeO Et 1 P-6 cPenMeO H 1Me-5-Ind P-2 A 4. 90 379 P-7 cPenMeO Et 1 Me-5-lnd P-8 cPenMeO H 5-1 HIdz P-9 cPenMeO Et 5-1 HIdz P-1 P-10 cPenMeO H 1Me-5-1HIdz P-2 P-11 cPenMeO Et 5-Bzt P-1 P-12 cPenMeO H 5-Bzt P-2 P-13 cPenMeO Et 5-2ABzt P-1 P-14 cPenMeO H 5-2ABzt P-2 Tr% P-15 H 6-IQ P-2 C P-16 cPenO H 2-Nap P-1, P-2 l P-17 cPenO H 5-Ind P-1, P-2 C P-18 cPenO H 1 P-2 P-19 cPenO H 5-1 P-2 P-20 cPenO H 1 P-2 P-21 cPenO H 5-Bzt P-1. P-2 P-22 cPenO H 5-2ABzt P-1, P-2 P-23 cHexO H 2-Nap P-1, P-2 A 5. 51 376 (M++1) P-24 cHexO. H 5-Ind P-1, P-2 P-25 cHexO H 1 P-26 cHexO H 1 P-2 P-27 2EtBuO H 2-Nap P-1, P-2 A 5. 68 378 (M++1) P-28 2EtBuO H 5-Ind P-1, P-2 P-29 2EtBuO H 1 P-2 P-30 iBuO H 2-Nap P-1, P-2 A 5. 13 350 (M++1) P-31 iBuO H 5-Ind P-1, P-2 P-32 iBuO H 1 P-1, P-2 P-33 iBuO P-34 BnO H 2-Nap P-1, P-2 P-35 BnO H 1Me-5-Ind P-36 (R) l Et 2-Nap P-36 P-37 (R) lPhEtO H 2-Nap P-37 P-38 (S) l H 2-Nap P-36, P37 A 5. 31 398 (M++1) P-39 (S) H 1 4. 75 401 (M++1) P-40 2MeBnO H 2-Nap P-1, P-2 P-41 2MeBnO H 1 P-2 OTable-P-2 P-42 4CF3BnO Et 2-Nap P-42 P-43 4CF3BnO H 2-Nap P-43 A 5. 52 452 (M++1) P-44 4CF3BnO H 1 P-2 P-45 3PhBuO H 1Me-5-Ind P-2 P-46 2 (2-Nap) EtO H 2-Nap P-2 P-47 2 (2-Nap) EtO H 1 P-2 P-48 2 (2FPh) EtO H P-49 2 (2FPh) EtO H 5-Ind P-1, P-2 A 4. 18 405 (M++1) P-50 2 (2FPh) EtO H 1 [Example Q-1] Synthesis of methyl 3- [4-methoxy-3- (naphthalen-2-yl)-5-nitrophenyl] propionate (Intermediate 49) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 15 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 10: 1), Intermediate 21 (2.65 g), 2-naphthaleneboronic acid (2.87 g), 2 M aqueous sodium carbonate (7.5 ml) and (Ph3P) 4Pd (960 mg) were reacted and treated to obtain the title compound (Intermediate 49,2. 47 g).
Synthesis of 3- [4-methoxy-3- (naphthalen-2-yl)-5-nitrophenyl] propionic acid (Intermediate 50) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 40 minutes, Intermediate 49 (2.45 g) and 2 N aqueous sodium hydroxide (6.7 ml) were reacted and treated to obtain the title compound (Intermediate 60,1. 96 g).
Synthesis of methyl 3- [4-hydroxy-3- (naphthalen-2-yl)-5-nitrophenyl] propionate (Intermediate 51) According to the procedure described in the synthesis method of Intermediate 10 provided that the reaction was carried out for 3 hours, pyridine (10 ml), concentrated hydrochloric acid (10 ml), and Intermediate 50 (1.00 g) were reacted and treated to obtain crude powder substance. This substance was reacted with thionyl chloride (282 u 1) in methanol and treated according to the procedure described in the synthesis method of Intermediate 1 to obtain the title compound (Intermediate 51,306 mg).
Synthesis of methyl 3- [4-cyclopentyloxy-3- (naphthalen-2-yl)-5- nitrophenyl] propionate (Compound No. Q-1) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 15.5 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 19: 1), Intermediate 51 (84 mg), Ph3P (125 mg), cyclopentanol (50 u 1) and 40% DIAD (224, u l) were reacted and treated to obtain the title compound (Compound No. Q-1, 90 mg).
[Example Q-2] Synthesis of methyl 3- [3-amino-4-cyclopentyloxy-5-(naphthalen-2- yl) phenyl] propionate (Compound No. Q-2) A solution of Compound No. Q-1 (59.1 mg) in methanol (5 ml) was added with platinum oxide (5 mg, Ald), and stirred at room temperature for 30 minutes under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 4 : 1) to obtain the title compound (Compound No. Q-2, 49 mg).
[Example Q-3] Synthesis of 3- [3-amino-4-cyclopentyloxy-5- (naphthalen-2-yl) phenyl] propionic acid (Compound No. Q-3) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. Q-2 (40 mg) and 2 N aqueous sodium hydroxide (150 u 1) were reacted and treated to obtain the title compound (Compound No. Q-3, 38 mg).
[Example Q-4] Synthesis of methyl 3- [4-cyclopentyloxy-3-(lH-indol-5-yl)-5-nitrophenyl] propionate (Compound No. Q-4) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 16 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 4 : 1), Compound No. A-28 (187 mg), 5-indoleboronic acid (143 mg), 2 M aqueous sodium carbonate (400, u 1) and (PhsP) 4Pd (51 mg) were reacted and treated to obtain the title compound (Compound No. Q-4,192 mg).
[Example Q-5] Synthesis of methyl 3-13-amino-4-cyclop entyloxy-5- (lH-indol-5-yl) phenyl] propionate (Compound No. Q-5) According to the procedure described in the synthesis method of Compound No. Q-2 with the modification that the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 2 : 1), Compound No. Q-4 (59.1 mg) and platinum oxide (5 mg) were reacted and treated to obtain the title compound (Compound No. Q-5,49. 3 mg).
[Example Q-6] Synthesis of 3- [3-amino-4-cyclopentyloxy-5- (lH-indol-5-yl) phenyl] propionic acid (Compound No. Q-6) According to the procedure described in the synthesis method of Intermediate 9, Compound No. Q-5 (44 mg) and 2 N aqueous sodium hydroxide (150 iL 1) were reacted and treated to obtain the title compound (Compound No. Q-6, 41 mg).
[Example Q-8] Synthesis of methyl 3- [4-cyclopentyloxy-3- (l-methyl-lH-indazol-5-yl)-5- nitrophenyl] propionate (Compound No. Q-8) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 16 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 3:1), Compound No. A-28 (182 mg), 1-methyl-5- indazoleboronic acid (152 mg), 2 M aqueous sodium carbonate (400, u 1) and (Ph3P) 4Pd (58.9 mg) were reacted and treated to obtain the title compound (Compound No. Q-8, 181 mg).
[Example Q-9] Synthesis of methyl 3- [3-amino-4-cyclopentyloxy-5- (1-methyl-lH-indazol-5- yl) phenyl] propionic acid (Compound No. Q-9) A solution of Compound No. Q-8 (578 mg) in a mixture of ethyl acetate (2 ml) and methanol (5 ml) was added with Raney 2800 nickel (230 mg) and stirred at room temperature for 6 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane : ethyl acetate 2 : 1) to obtain the title compound (Compound No. Q-9, 484 mg).
[Example Q-10] Synthesis of 3- [3-amino-4-cyclopentyloxy-5- (lH-indazol-5-yl) phenyl] propionic acid (Compound No. Q-10) According to the procedure described in the synthesis method of Intermediate 9, Compound No. Q-9 (56 mg) and 2 N aqueous sodium hydroxide (200 , u 1) were reacted and treated to obtain the title compound (Compound No. Q-10, 50 mg).
[Example Q-47] Synthesis of methyl 3- [4-benzyloxy-3- (naphthalen-2-yl)-5-nitrophenyl] propionate (Compound No. Q-47) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 12 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 8: 1), Compound No. B-95 (6.00 g), 2-naphthaleneboronic acid (4.11 g), 2 M aqueous sodium carbonate (13.5 ml) and (Ph3P) 4Pd (1.36 g) were reacted and treated to obtain the title compound (Compound No. Q-47, 5.81 g).
[Example Q-48] Synthesis of methyl 3- [3-amino-4-benzyloxy-5- (naphthalen-2-yl) phenyl] propionate (Compound No. Q-48) According to the procedure described in the synthesis method of Compound No. Q-9 with the modifications that the reaction was carried out for 20 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 2: 1), Compound No. Q-47 (5.04 g) and Raney 2800 nickel (2.50 g) were reacted and treated to obtain the title compound (Compound No. Q-48, 4.21 g).
[Example Q-1 to Q-52] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-Q-1. zx Rx-\//0-Y ex Table-Q-1 AR Exp. RxO Y Zx AR Syn LCMS"" method Mass Q-1 cPenO 2-Nap Q-1 Q-2 cPenO Me NH2 2-Nap Q-2 Q-3 cPenO H NH2 2-Nap Q-3 A 4. 78 376 Q-4 cPenO Me N02 5-Ind Q-4 Q-5 cPenO Me NH2 5-Ind Q-6 cPenO H NH2 5-land Q-6 A 3. 75 365 (M++1) Q-7 cPenO H NH2 1 Me-5-Ind Q-6 A 4. 19 379 (M++1) Q-8 cPenO Me N02 1 Q-8 Q-9 cPenO. Me NH2 1 Q-10 cPenO H NH2 1 Q-11 H NH2 5-1 Q-12 H NH2 5-Bzt Q-8, Q-9, Q-10 Q-13 cPenO H NH2 5-2ABzt Q-8, Q-9, Q-10 Q-14 cPenO H NH2 2Me-5-Bzt Q-15 cHexO H NH2 2-Nap Q-1, Q-2, Q-3 A 5. 66 404 (M++1) Q-16 cHexO H NH2 1 Me-5-Ind Q-6 Q-17 cHexO H NH2 1 Q-18 H NH2 2-Nap Q-1, Q-2, Q-3 Q-19 H NH2 5-Ind Q-6 A 4. 26 381 (M++1) Q-20 2EtBuO H NH2 1 Me-5-Ind Q-6 Q-21 2EtBuO H NH2 5-1 Q-8, Q-9, Q-10 Q-22 2EtBuO H NH2 1 Q-23 2EtBuO H NH2 5-Bzt Q-8 Q-9. Q-10 Q-24 2EtBuO H NH2 5-2ABzt Q-8, Q-9. Q-10 Q-25 2EtBuO H NH2 2Me-5-Bzt Q-8 Q-9 Q-10 Q-26 iBuO H NH2 2-Nap Q-1, Q-2, Q-3 A 4. 82 364 (M++1) Q-27 iBuO H NH2 1 Me-5-Ind Q-6 Q-28 iBuO H NH2 1 A 3. 66 368 (M++1) Q-29 (S) 1 H NH2 2-Nap Q-1, Q-2, Q-3 A 4. 87 412 (M++1) Q-30 (S) 1 H NH2 1 Me-5-Ind Q-6 A 4. 31 415 (M++1) Q-31 (S) 1 H NH2 1 Q-10 A 3. 76 416 Q-32 4CF3BnO H NH2 2-Nap Q-1, Q-2, Q-3 A 5. 26 466 (M++1) Q-33 4CF3BnO H NH2 1 Q-6 A 4. 20 455 (M++1) Q-34 4CF3BnO H NH2 l Q-35 2-IndanO H NH2 2-Nap Q-1, Q-2, Q-3 A 5. 10 424 (M++1) Q-36 2-IndanO H NH2 1 Q-6 A 4. 63 Q-37 2-IndanO H NH2 1 A 4. 14 428 Q-38 5OMe-2-IndanO H NH2 2-Nap Q-1, Q-2, Q-3 Q-39 5, 6 (OMe)-2-lndano H NH2 1 Q-6 Q-40 5F-2-IndanO H NH2 1 Q-41 2 (4FPh) EtO H NH2 2-Nap Q-1, Q-2, Q-3 Q-42 2 (4FPh) EtO H NH2 1 Q-43 2 (4FPh) EtO H NH2 1 A 4. 48 448 (M++1) Q-44 2 (4DMAPh) EtO H NH2 2-Nap Q-1, Q-2, Q-3 A 4. 28 455 Q-45 2 (4DMAPh) EtO H NH2 1 Q-46 2 (4DMAPh) EtO H NH2 1 A 3. 12 459 (M++1) Q-47 Me N02 2-Nap Q-47 Q-48 BnO Me NH2 2-Nap Q-48 Q-49 BnO H NH2 2-Nap Q-3 Q-50 BnO Me N02 1 Q-47 a Me NH2 1 Q-52 [Example S-1] Synthesis of methyl 3- {4-benzyloxy-3- (naphthalen-2-yl) -5- [N- (2, 2,2- trifluoroacetyl) amino] phenyl} propionate (Intermediate 52) According to the procedure described in the synthesis method of Compound No. B-103 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 4: 1), Compound No. Q-48 (4. 18 g), triethylamine (4.65 ml) and trifluoroacetic anhydride (7.40 ml) were reacted and treated to obtain the title compound (Intermediate 52,4. 72 g).
Synthesis of methyl 3- {4-hydroxy-3- (naphthalen-2-yl)-5- [N- (2, 2,2- trifluoroacetyl) amino] phenyl} propionate (Intermediate 53) A solution of Intermediate 52 (3.20 g) in a mixture of ethyl acetate (50 ml) and methanol (25 ml) was added with 10% palladium/carbon (98 mg), and stirred at room temperature for 2 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Intermediate 53, 2. 39 g).
Synthesis of methyl 3- {4-cyclopentyloxy-3- (naphthalen-2-yl)-5- [N- (2, 2,2- trifluoroacetyl) amino] phenyl} propionate (Intermediate 54) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 15.5 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 19 : 1), Intermediate 53 (84 mg), PhsP (125 mg), cyclopentanol (50 u 1) and 40% DIAD (224, u 1) were reacted and treated to obtain the title compound (Intermediate 54,90 mg).
Synthesis of methyl 3- {4-cyclopentyloxy-3- [N-methyl-N- (2, 2,2- trifluoroacetyl) amino]-5- (naphthalen-2-yl) phenyl} propionate (Intermediate 55) A solution of Intermediate 54 (208 mg) in DMF (5 ml) was added with 60% sodium hydride (21 mg) under ice cooling, and stirred for 20 minutes. This reaction mixture was added dropwise with methyl iodide (150, u 1), stirred for 10 minutes, then warmed to room temperature, and further stirred for 1 hour. The reaction mixture was poured into ice water, and ethyl acetate (100 ml) was added for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 5 : 1) to obtain the title compound (Intermediate 55,200 mg).
Synthesis of 3- [4-cyclopentyloxy-3-(N-methylamino)-5- (naphthalen-2- yl) phenyl] propionic acid (Compound No. S-1) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 6 hours, Intermediate 55 (198 mg) and 2 N aqueous sodium hydroxide (800 u 1) were reacted and treated to obtain the title compound (Compound No. S-1, 38 mg).
[Example S-3] Synthesis of methyl 3- [3-acetylamino-4-cyclopentyloxy-5- (naphthalen-2- yl) phenyl] propionate (Compound No. S-3) A solution of Compound No. Q-2 (81 mg) in methylene chloride (2 ml) was added with N-methylmorpholine (33, u l, WAKO), and added with acetyl chloride (22, u 1) under ice cooling. The reaction mixture was stirred for 10 minutes, then warmed to room temperature, and further stirred for 18 hours. The reaction mixture was poured into aqueous sodium hydrogencarbonate (100 ml), and added with ethyl acetate (150 ml) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 6: 1) to obtain the title compound (Compound No. S-3,85 mg).
[Example S-4] Synthesis of 3- [3-acetylamino-4-cyclopentylmethyloxy-5- (naphthalen-2- yl) phenyl] propionic acid (Compound No. S-4) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 15 hours, Compound No. S-3 (80 mg) and 2 N aqueous sodium hydroxide (400 t 1) were reacted and treated to obtain the title compound (Compound No. S-4, 75 mg).
[Example S-5] Synthesis of 3- [4-cyclopentyloxy-3-formylamino-5- (naphthalen-2- yl) phenyl] propionic acid (Compound No. S-5) A solution of Compound No. Q-2 (90 mg) in DMF (5 ml) was added with a mixture of formic acid (200 u 1) and acetic anhydride (100, u 1) under ice cooling.
The reaction mixture was stirred 10 minutes, then warmed to room temperature, and further stirred for 18 hours. The reaction mixture was poured into aqueous sodium hydrogencarbonate (100 ml), and added with ethyl acetate (150 ml) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 5: 1). The obtained substance was reacted and treated with 2N aqueous sodium hydroxide (400 u 1) according to the procedure described in the synthesis method of Intermediate 9 to obtain the title compound (Compound No. S-5,65 mg).
[Example S-6] Synthesis of methyl 3- [3- (2-acetoxyacetylamino)-4-cyclopentyloxy-5- (naphthalen-2- yl) phenyl] propionate (Compound No. S-6) According to the procedure described in the synthesis method of Intermediate 70, Compound No. Q-2 (88 mg), N-methylmorpholine (36 A 1) and acetoxyacetyl chloride (35 u 1, Ald) were reacted and treated to obtain the title compound (Compound No. S-6, 75 mg).
[Example S-7] Synthesis of 3- [4-cyclopentyloxy-3- (2-hydroxyacetylamino) -5- (naphthalen-2- yl) phenyl] propionic acid (Compound No. S-7) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 15.5 hours, Compound No. S-6 (102 mg) and 2 N aqueous sodium hydroxide (500 u 1) were reacted and treated to obtain the title compound (Compound No. S-7,80 mg).
[Example S-8] Synthesis of 3- [3-carbamoylamino-4-cyclopentyloxy-5- (naphthalen-2- yl) phenyllpropionic acid (Compound No. S-8) A solution of Compound No. Q-2 (100 mg) in a mixture of acetic acid (2 ml) and purified water (0.4 ml) was added with potassium cyanate (45 mg, Wako Pure Chemical Industries), and stirred at room temperature for 1 hour. The reaction mixture was poured into water (50 ml) containing ice, and extracted with isopropyl ether (150 ml x 2). The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The obtained substance was reacted with 2 N aqueous sodium hydroxide (300, jeu 1) and treated according to the procedure described in the synthesis method of Intermediate 9 to obtain the title compound (Compound No. S-8, 70 mg).
[Example S-9] Synthesis of methyl 3- [4-cyclopentyloxy-3-methylsulfonylamino-5- (naphthalen-2- yl) phenyl] propionate (Compound No. S-9) A solution of Compound No. Q-2 (81 mg) in methylene chloride (2 ml) was added with pyridine (300 u 1), and then added with methanesulfonyl chloride (40 u 1) under ice cooling. The reaction mixture was stirred for 10 minutes, then warmed to room temperature, and further stirred for 2 hours. The reaction mixture was poured into 1 N hydrochloric acid, and added with ethyl acetate (150 ml) for extraction. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, and saturated brine, and dried, and then the solvent of the organic layer was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 13: 2) to obtain the title compound (Compound No. S-9, 96 mg).
Synthesis of 3- [4-cyclopentyloxy-3-methylsulfonylamino-5- (naphthalen-2- yl) phenyl] propionic acid (Compound No. S-10) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out at room temperature for 17.5 hours and at 60°C for 3 hours, Compound No. S-9 (81 mg) and 2 N aqueous sodium hydroxide (400 u 1) were reacted and treated to obtain the title compound (Compound No. S-10,80 mg).
[Example S-11] Synthesis of 3- [4-cyclopentyloxy-3- (N, N-dimethylsulfamoylamino)-5- (naphthalen-2- yl) phenyl] propionic acid (Compound No. S-11) A solution of Compound No. Q-2 (163 mg) in pyridine (5 ml) was successively added with 4-dimethylaminopyridine (104 mg, TCI) and dimethylsulfamoyl chloride (520 g 1, TCI), and stirred for 5 days. The reaction mixture was added with water (30 ml) and ethyl acetate (90 ml) for extraction.
The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 6: 1). The obtained substance was reacted with 2 N aqueous sodium hydroxide (300 u 1) and treated according to the procedure described in the synthesis method of Intermediate 9 to obtain the title compound (Compound No. S-11, 105 mg).
[Example S-12] Synthesis of 3- [4-cyclop entyloxy-3- (N, N-dimethylamino)-5- (nap hthalen-2- yl) phenyl] propionic acid (Compound No. S-12) A solution of Compound No. Q-2 (60 mg) in DMF (3 ml) was added with 60% sodium hydride (26 mg) under ice cooling, and stirred for 10 minutes. The reaction mixture was added with methyl iodide (100 je 1), stirred for 10 minutes, then warmed to 60°C, and further stirred for 2 hours. The reaction mixture was poured into water (20 ml), and ethyl acetate (50 ml) was added for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 8: 1). The obtained substance was reacted with 2 N aqueous sodium hydroxide (150, A 1) and treated according to the procedure described in the synthesis method of Intermediate 9 to obtain the title compound (Compound No. S-12,46 mg).
Synthesis of methyl 3- {4-benzyloxy-3- (l-methyl-lH-indazol-5-yl)-5- [N- (2,2, 2- trifluoroacetyl) amino] phenyl} propionate (Intermediate 56) According to the procedure described in the synthesis method of Compound No. B-103 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 3: 1), Compound No. Q-51 (2.09 g), triethylamine (3.70 ml) and trifluoroacetic anhydride (2.35 ml) were reacted and treated to obtain the title compound (Intermediate 56,2. 36 g).
Synthesis of methyl 3- {4-hydroxy-3- (l-methyl-lH-indazol-5-yl)-5- [N- (2,2, 2- trifluoroacetyl) amino] phenyl} propionate (Intermediate 57) A solution of Intermediate 56 (1.62 g) in a mixture of ethyl acetate (10 ml) and methanol (3 ml) was added with 10% palladium/carbon (29 mg), and stirred at room temperature for 17 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Intermediate 57,1. 19 g).
[Examples S-1 to S-73] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-S-1 and Table-S-2. Zx Rx-O air Table-S-1 _. -., LCMS method S-1 cPenO H S-1 S-2 cPenO H NHEt 2-Nap S-1 S-3 cPenO Me NHAc 2-Nap S-3 S-4 cPenO H NHAc 2-Nap S-4 C S-5 cPenO H NHCHO 2-Nap S-5 C S-6 S-8 S-7 cPenO H NHCOCH2OH 2-Nap S-7 C 437 (M++1) S-8 cPenO H NHCONHa 2-Nap S-8 C 422 (M++1) S-9 cPenO Me NHSO2Me 2-Nap S-9 S-10 cPenO H NHSO2Me 2-Nap S-10 C S-11 cPenO H NHSO2NMe2 2-Nap S-11 C483 S-12 cPenO H NMe2 2-Nap S-12 S-13 cPenO H NHMe 1 Me-5-Ind S-1 S-14 cPenO H NMe2 1 S-12 C S-15 cPenO H NHMe 1 S-16 cPenO H NMe2 1 S-12 S-17 cPenO H NHMe 5-Bzt S-1 S-18 cPenO H NMe2 5-Bzt S-12 S-19 cPenO H NHMe 5-2ABzt S-1 S-20 cPenO H NMe2 5-2ABzt S-12 S-21 cPenO H NHMe 2Me-5-Bzt S-1 S-22 cPenO H NMe2 2Me-5-Bzt S-12 S-23 cPenMeO H S-1 S-24 cPenMeO H NMe2 S-12 S-25 cPenMeO H NHME S-26 cPenMeO H NMe2 1 S-27 cHexO H NHMe 2-Nap S-1 S-28 cHexO H NMe2 2-Nap S-12 S-29 cHexO H NHMe 1 S-1 C S-30 cHexO H NMe2 1 S-12 S-31 cHexO H NHMe 1 S-1 S-32 cHexO H NMe2 1 Me-5-1 Hldz S-33 2EtBuO H NHMe 2-Nap S-1 C S-34 2EtBuO H NHMe 6-OMe-2-Nap S-1 S-35 2EtBuO H NHMe 1 S-1 S-36 2EtBuO H NHMe 5-Bzt S-1 S-37 2EtBuO H NHMe 1 S-1 S-38 iBuO H NHMe 2-Nap S-1 S-39 iBuO H NMe2 2-Nap S-12 C 392 (M++1) S-40 H NHMe 1 S-1 C S-41 iBuO H NMe 1 Me-5-Ind S-12 S-42 iBuO H NHMe 1 S-43 iBuO H NMez S-12 S-44 lPhEtO S-45'1 X fYTable-S-2 S-46 1 H NHMe 1 S-1 S-47 1 S-48 1 H NHMe 1 S-1 C S-49 H NMea 1 S-12 S-50 4CF3BnO H NHMe 2-Nap S-1 S-51 40FsBnO 2-Nap S-12 S-52 4CF3BnO H NHMe 1 S-53 4CF3BnO H NMe2 1 S-12 C S-54 4CF3BnO H NHMe 1Me-5-1HIdz S-55 4CF3BnO H NMe2 1 S-12 S-56 2-IndanO H NHMe S-1 S-57 2-IndanO H NMe2 2-Nap S-12 S-58 2-IndanO H NHMe 1 S-1 C441 +1) S-59 2-IndanO H NMe2 1 S-12 S-60 2-IndanO H NHMe 1 A 4. 16 442 (M++1) S-61 2-IndanO H NMe2 1 S-12 A 4. 18 456 (M++1) S-62 2 (4FPh) EtO H NHMe 2-Nap S-1 S-63 2 (4FPh) EtO H NMe2 2-Nap S-12 C S-64 2 (4FPh) EtO H NHMe 1 S-1 C S-65 2 (4FPh) EtO H NMe2 1Me-5-Ind S-66 2 (4FPh) EtO H NHMe 1 S-67 2 (4FPh) EtO H NMe2 1 S-12 S-68 2 (4DMAPh) EtO H NHMe 2-Nap S-1 C S-69 2 (4DMAPh) EtO H NMe2 2-Nap S-12 S-70 2 (4DMAPh) H NHMe 1 S-1 S-71 2 (4DMAPh) EtO H NMe2 1 S-72 2 (4DMAPh) EtO H NHMe t S-73 2 (4DMAPh) EtO H NMe2 1 Me-5-1 [Example T-1] Synthesis of 3- [4-cyclopentylmethyloxy-3-hydroxy-5- (naphthalen-2- yl) phenyl) propionic acid (Compound No. T-1) A solution of Compound No. Q-2 (403 mg) in acetic acid (1.5 ml) was added with 20% sulfuric acid (1.0 ml). This reaction mixture was added dropwise with an aqueous solution (0.5 ml) of sodium nitrite (76 mg) over 10 minutes while keeping the temperature of the reaction mixture below 10°C, and further stirred for 5 minutes. This reaction solution was added to a solution of sodium acetate (328 mg) in acetic acid (3.5 ml) heated and stirred at 100°C beforehand, and further stirred for 10 minutes with heating. The reaction solution was poured into ice water (50 ml), and extracted with isopropyl ether (100 ml x 2). The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10 : 1). The obtained substance was reacted with 2 N aqueous sodium hydroxide (500 u 1) and treated according to the procedure described in the synthesis method of Intermediate 9 to obtain the title compound (Compound No. T-1, 78 mg).
Example T-2] Synthesis of ethyl 3- [3-acetoxy-4-cyclopentyloxy-5- (naphthalen-2- yl) phenyl] propionate (Intermediate 58) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 9: 1), Compound No. B-114 (160 mg), 2-naphthaleneboronic acid (382 mg, Ald), 2 M aqueous sodium carbonate (0.7 ml) and (Ph3P) 4Pd (105 mg) were reacted and treated to obtain the title compound (Intermediate 58,152 mg).
Synthesis of 3- [4-cyclopentyloxy-3-hydroxy-5- (naphthalen-2-yl) phenyl] propionic acid (Compound No. T-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Intermediate 58 (146 mg) and 2 N aqueous sodium hydroxide (0.35 ml) were reacted and treated to obtain the title compound (Compound No. T-2,135 mg).
[Example T-31] Synthesis of ethyl 3- [4-cyclopentyloxy-3-methoxy-5- (naphthalen-2- yl) phenyl] propionate (Compound No. T-31) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 14 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 9 : 1), Compound No. A-25 (210 mg), 2-naphthaleneboronic acid (184 mg), 2 M aqueous sodium carbonate (0.5 ml) and (Ph3P) 4Pd (65.3 mg) were reacted and treated to obtain the title compound (Compound No. T-31, 181 mg).
[Example T-32] Synthesis of 3- [4-cyclopentyloxy-3-methoxy-5- (naphthalen-2-yl) phenyl] propionic acid (Compound No. T-32) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. T-31 (166 mg) and 2 N aqueous sodium hydroxide (0.45 ml) were reacted and treated to obtain the title compound (Compound No. T-32,135 mg).
[Example T-33] Synthesis of 4- (t-butyldimethylsilyloxy) -3- (lH-indol-5-yl)-5-methoxybenzaldehyde (Intermediate 59) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 12.5 hours, and the purification was performed by flash column chromatography (hexane: ethyl acetate = 7: 1), 5-indoleboronic acid (1.29 g), Intermediate 16 (1.75 g), 2 M aqueous sodium carbonate (4.8 ml) and (Ph3P) 4Pd (400 mg) were reacted and treated to obtain the title compound (Intermediate 59,910 mg).
Synthesis of ethyl 3- [4- (t-butyldimethylsilyloxy)-3- (lH-indol-5-yl)-5- methoxyphenyl] aerylate (Intermediate 60) According to the procedure described in the synthesis method of Intermediate 7 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by flash column chromatography (hexane: ethyl acetate = 3: 1), Intermediate 59 (910 mg), ethyl diethylphosphonoacetate (500, l) and 60% sodium hydride (100 mg) were reacted and treated to obtain the title compound (Intermediate 60,945 mg).
Synthesis of ethyl 3- [4- (t-butyldimethylsilyloxy)-3-(lH-indol-5-yl)-5- methoxyphenyl] propionate (Intermediate 61) According to the procedure described in the synthesis method of Intermediate 8, Intermediate 60 (945 mg) and 10% palladium/carbon (95 mg) were reacted and treated under hydrogen gas atmosphere to obtain the title compound (Intermediate 61,940 mg).
Synthesis of ethyl 3-L4-hydroxy-3- (lH-indol-5-yl)-5-methoxyphenyl] propionate (Intermediate 62) According to the procedure described in the synthesis method of Intermediate 19 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 2: 1), Intermediate 61 (750 mg) and a 1 M solution of tetrabutylammonium fluoride in THF (5.0 ml) were reacted and treated to obtain the title compound (Intermediate 62,555 mg).
Synthesis of ethyl 3- [4-cyclopentyloxy-3- (lH-indol-5-yl)-5- methoxyphenyl] propionate (Compound No. T-33) According to the procedure described in the synthesis method of Compound No. A-6 with the modifications that the reaction was carried out for 16 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 7: 1), Intermediate 62 (340 mg), PhsP (1.31 g), cyclopentanol (450 A 1) and TMAD (860 mg) were reacted and treated to obtain the title compound (Compound No. T-33,376 mg).
[Example T-34] Synthesis of 3- [4-cyclopentyloxy-3- (lH-indol-5-yl)-5-methoxyphenyl] propionic acid (Compound No. T-34) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. T-33 (99 mg) and 2 N aqueous sodium hydroxide (500, u 1) were reacted and treated to obtain the title compound (Compound No. T-34, 76 mg).
[Examples T-1 to T-61] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-T-1 and Table T-2. Zx 0 Table-T-1 _ Exp. RxO Y Zx AR Syn method T-1 cPenMeO H OH 2-Nap T-1 5. 03 382 (M++1) T-2 cPenO H OH T-3 cPenO H OH 5-Ind T-2 C 366 (M'+1) T-4 cPenO H OH 1 Me-5-Ind Int73, T-2 T-5 cPenO H OH 5-1 T-2 T-6 cPenO H OH 1 T-2 C T-7 cHexO H OH 2-Nap T-1 T-8 cHexO H OH 1 Me-5-Ind T-1 T-9 cHexO H OH 1 T-10 2EtBuO H OH 2-Nap T-1 _ T-11 OH I Me-5-Ind T-1 T-12 2EtBuO H OH 1 T-1 T-13 iBuO H OH 2-Nap T-1 T-14 iBuO H OH 1 Me-5-Ind T-15 iBuO H OH 1 Me-5-ldz T-1 T-16 H OH 2-Nap T-1 T-17 1 H OH 1 Me-5-Ind T-1 C T-18 1 H OH 1 T-1 T-19 4CF3BnO H OH 2-Nap T-1 T-20 4CF3BnO H OH 1 Me-5-Ind T-1 T-21 4CF3BnO H OH T-22 2-IndanO H OH 2-Nap T-1 T-23 2-IndanO H OH 1 Me-5-Ind T-1 T-24 2-IndanO H OH T-1 A 3. 91 429 (M++l) T-25 2 (4FPh) EtO H OH 2-Nap T-1 T-26 2 (4FPh) EtO H OH 1Me-5-Ind T-27 2 (4FPh) EtO H OH 1Me-5-Idz T-1 T-28 2 H OH 2-Nap T-1 T-29 2 (4DMAPh) EtO H OH I T-30 2 H OH T-1 T-31 cPenO Et OMe 2-Nap T-31 T-32 cPenO H OMe 2-Nap T-32 T-33 cPenO Et OMe 5-Ind T-34 cPenO H OMe 5-Ind T-34 T-35 cPenO H OMe 1 Me-5-Ind T-33, 4. 72 394 (M++1) T-36 cPenO H OMe 5-1 T-32 T-37 cPenO H OMe 1 T-38 cHexO H OMe 2-Nap T-31, T-32 C T-39 cHexO H OMe 1 Me-5-Ind T-33, T-34 T-40 cHexO H OMe 1Me-5-Idz T-32 T-41 2EtBuO H OMe 2-Nap T-31, T-32 T-42 2EtBuO H OMe 1 Me-5-Ind T-33, T-34 T-43 2EtBuO H OMe 1 ARTable-T-2 T-44 iBuO H OMe 2-Nap T-31, T-32 T-45 iBuO H OMe 1 T-34 C 382 (M++1) T-46 iBuO H OMe 1 T-47 I H OMe 2-Nap T-31. T-48 1 H OMe 1 T-49 1 H OMe 1 T-32 C T-50 4CF3BnO H OMe 2-Nap T-31, T-32 T-51 4CF3BnO H OMe 1 T-34 T-52 4CF3BnO H OMe T-32 T-53 2-IndanO H OMe 2-Nap T-31, T-32 T-54 2-IndanO H OMe 1 T-34 T-55 2-IndanO H OMe T-32 C T-56 2 (4FPh) EtO H OMe 2-Nap T-31, T-57 2 (4FPh) EtO H OMe 1 T-34 C T-58 2 (4FPh) EtO H OMe 1Me-5-1H T-59 2 (4DMAPh) EtO H OMe 2-Nap T-31, T-32 C T-60 2 (4DMAPh) EtO H OMe 1Me-5-Ind T-61 2 H OMe 1 T-32 [Example tJ-1] Synthesis of 4-cyclohexylmethyloxy-3- (naphthalen-2-yl) phenylacetonitrile (Intermediate 63) A solution of Compound No. C-1 (172 mg) in dehydrated THF (5 ml) was added successively with trimethylsilylnitrile (133 u 1, TCI) under ice cooling and zinc iodide (16 mg, WAKO) under argon gas atmosphere, stirred for 15 minutes, then warmed to room temperature, and further stirred for 27 hours. The reaction mixture was added with ethyl acetate (90 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. A solution of the residue in anhydrous methylene chloride (5 ml) was added with triethylsilane (240/ 1, TCI) under ice cooling and boron trifluoride diethyl ether complex (366 1, TCI) under argon gas atmosphere, warmed to room temperature, and stirred for 3.5 hours. The reaction mixture was poured into ice water (50 ml), and extracted with ethyl acetate (90 MI).
The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10: 1) to obtain the title compound (Intermediate 63,116 mg).
Synthesis of 4-cyclohexylmethyloxy-3- (naphthalen-2-yl) phenylacetic acid (Compound No. U-1) According to the procedure described in the synthesis method of Intermediate 9 with the modifications that the reaction was carried out for 24 hours under reflux by heating, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 2: 1), Intermediate 63 (110 mg) and 5 N aqueous sodium hydroxide (900, it 1) were reacted and treated to obtain the title compound (Compound No. U-1, 62 mg).
[Example U-10] Synthesis of methyl 4- [4-cyclopentylmethyloxy-3- (nap hthalen-2-yl) phenyl] butyrate (Compound No. U-10) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 18 hours, and the purification was performed by column chromatography (Quad, hexane : isopropyl ether = 8: 1), Compound No. F-1 (355 mg), 2-naphthaleneboronic acid (344 mg), 2 M aqueous sodium carbonate (2.1 ml) and (Ph3P) 4Pd (115 mg) were reacted and treated to obtain the title compound (Compound No. U-10, 392 mg).
[Example U-11] Synthesis of 4- [4-cyclopentylmethyloxy-3- (naphthalen-2-yl) phenyl] butyric acid (Compound No. U-11) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3.5 hours, Compound No. U-10 (380 mg) and 2 N aqueous sodium hydroxide (1.0 ml) were reacted and treated to obtain the title compound (Compound No. U-11, 342 mg).
Examples U-1 to U-18] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-U-1. Z Rx-O< srs Table _ Exp. RxO Y Zx n AR Syn LCMS method Mass U-1 cHexMeO H H 1 2-Nap U-1 C U-2 cHexMeO H H U-1 U-3 cHexMeO H H 1 iMe-5-ldz U-4 cPenMeO H H 2-Nap Int63, U-1 C U-5 cPenMeO H H 1 U-1 U-6 cPenO H H 1 2-Nap Int63, U-1 U-7 cPenO H H 1 1 U-1 C U-8 2 (4FPh) EtO H H 1 2-Nap Int63. U-1 U-9 2 (4FPh) EtO H H 1 1 U-1 U-10 cPenMeO Me H 3 2-Nap U-10 C U-11 H 3 2-Nap U-11 U-12 H H 3 1 U-13 cPenO H 3 2-Na U-14 H H 3 1Me-5-Ind U-10, U-15 cHexO H H 3 2-Nap U-10, U-11 U-16 cHexO H H 3 1 U-17 2 (4FPh) EtO H H U-18 2 (4FPh) Et0 (CH2kCOOYExample V-1] Synthesis of ethyl 3- [4-cyclohexylmethyloxy-3-(naphthalen-1-yl) phenyl] acrylate (Intermediate 64) According to the procedure described in the synthesis method of Intermediate 7 provided that the reaction was carried out for 1 hour, Compound No.
C-2 (361 mg), ethyl diethylphosphonoacetate (240, u 1), 60% sodium hydride (69 mg) were reacted and treated to obtain the title compound (Intermediate 64,377 mg).
Synthesis of ethyl 3- [4-cyclohexylmethyloxy-3-(naphthalen-l-yl) phenyl] propionate (Compound No. V-1) According to the procedure described in the synthesis method of Intermediate 8 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 10 : 1), Intermediate 64 (361 mg) and 10% palladium/carbon (49 mg) were reacted under hydrogen atmosphere and treated to obtain the title compound (Compound No. V-1, 344 mg).
[Example V-2] Synthesis of 3- [4-cyclohexylmethyloxy- 3- (naphthalen-I-yl) p henyllp rop ionic acid (Compound No. V-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1.5 hours, Compound No. V-1 (332 mg) and 2 N aqueous sodium hydroxide (900 A 1) were reacted and treated to obtain the title compound (Compound No. V-2, 295 mg).
[Example V-3] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (6-hydroxynaphthalen-2- yl) phenyl] propionate (Compound No. V-3) A solution of 2-bromo-6-hydroxynaphthalene (243 mg, TCI) in anhydrous THF (10 ml) was cooled to-78°C, added dropwise with a 1.6 M solution of n- butyllithium in hexane (1.18 ml) over 20 minutes under argon gas atmosphere, and stirred for 30 minutes. The reaction mixture was added dropwise with (iPrO) 3B (1.73 ml) over 10 minutes, stirred for 30 minutes, then warmed to room temperature, and further stirred for 2 hours. The reaction mixture was added with 0.5 M aqueous sulfuric acid (2 ml), and extracted with diethyl ether (40 ml x 3).
The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude 6-hydroxy-2- naphthaleneboronic acid (378 mg). A solution of this substance in ethanol (1 ml), Compound No. A-1 (230 mg), and 2 M aqueous sodium carbonate (2.4 ml) were added with toluene (3 ml) and (Ph3P) 4Pd (115 mg) and stirred at 100°C for 13 hours.
The reaction mixture was added with ethyl acetate (100 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 6: 1) to obtain the title compound (Compound No. V-3, 270 mg).
[Example V-41 Synthesis of 3- [4-cyclopentylmethyloxy-3- (6-hydroxynaphthalen-2- yl) phenyl] propionic acid (Compound No. V-4) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 14 hours, Compound No. V-3 (149 mg) and 2 N aqueous sodium hydroxide (370 u 1) were reacted and treated to obtain the title compound (Compound No. V 4, 117 mg).
[Example V-5] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (5-hydroxynaphthalen-2- yl) phenyl] propionate (Compound No. V-5) 2-Amino-5-hydroxynaphthalene (4.80 g, TCI) was dissolved in 6 N hydrochloric acid (300 ml), added dropwise with an aqueous solution (22.5 ml) of sodium nitrite (2.25 g) over 30 minutes under ice cooling, and stirred for 30 minutes. The reaction mixture was added dropwise with an aqueous solution (75 ml) of potassium iodide (9.90 g, WAKO), stirred for 30 minutes, then warmed to room temperature, and further stirred for 3.5 hours. The reaction mixture was neutralized with aqueous ammonia, and then filtered through a Celite layer. The filtrate was added with ethyl acetate (90 ml x 2) for extraction. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 10 : 1) to obtain l-hydroxy-6- iodonaphthalene (1.48 g). A solution of this substance (539 mg) in anhydrous THF (10 ml) was added with 60% sodium hydride (171 mg) under ice cooling, and stirred for 1 hour. The reaction mixture was cooled to-78°C under argon gas atmosphere, added dropwise with a 1.6 M solution of n-butyllithium in hexane (3.75 ml) over 10 minutes, and stirred for 30 minutes. The reaction mixture was added dropwise with (iPrO) 3B (1.16 ml) over 10 minutes, stirred for 30 minutes, then warmed to room temperature, and further stirred for 3 hours. The reaction mixture was added with water (3 ml) and 0.5 M aqueous sulfuric acid (7 ml), and extracted with diethyl ether (100 ml x 3). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude 7-hydroxy-2-naphthaleneboronic acid. A solution of this substance in ethanol (1 ml), Compound No. A-1 (350 mg), 2 M aqueous sodium carbonate (2.4 ml) and (Ph3P) 4Pd (116 mg) were reacted and treated according to the procedure described in the synthesis method of Compound No. V-3 with the modifications that the reaction was carried out for 14 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 6: 1) to obtain the title compound (Compound No. V 5, 388 mg).
[Example V-6] Synthesis of 3-14-cyclopentylmethyloxy-3- (5-hydroxynaphthalen-2- yl) phenyl] propionic acid (Compound No. V-6) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 12 hours, Compound No. V-5 (355 mg) and 2 N aqueous sodium hydroxide (1. 75 ml) were reacted and treated to obtain the title compound (Compound No. V-6, 158 mg).
[Example V-7] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (7-hydroxynaphthalen-2- yl) phenyl] propionate (Compound No. V-7) According to the procedure described in the synthesis method of Compound No. V-5 with the modifications that the reaction was carried out for 4 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 6 : 1), crude 7-hydroxy-2-naphthaleneboronic acid prepared from 2-bromo- 7-hydroxynaphthalene (559 mg, MAYB), a 1.6M solution of n-butyllithium in hexane (3.91 ml) and (iPrO) sB (1.16 ml), Compound No. A-1 (386 mg), 2 M aqueous sodium carbonate (4.0 ml) and (Ph3P) 4Pd (195 mg) were reacted and treated to obtain the title compound (Compound No. V-7,460 mg).
[Example V-8] Synthesis of 3- [4-cyclopentylmethyloxy-3- (7-hydroxynaphthalen-2- yl) phenyl] propionic acid (Compound No. V-8) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 27 hours, Compound No. V-7 (176 mg) and 2 N aqueous sodium hydroxide (436, u 1) were reacted and treated to obtain the title compound (Compound No. V-8, 109 mg).
[Example V-11] Synthesis of methyl 3- 4-cyclohexylmethyloxy-3- [6- (N, N- dimethylcarbamoylmethyloxy) naphthalen-2-yl] phenyllpropionate (Compound No. V- 11) A solution of Compound No. V-3 (185 mg) in DMF (5 ml) was added with potassium carbonate (274 mg), and 2-chloro-N, N-dimethylacetamide (411 1, KANTO), and stirred at 50°C for 18 hours. The reaction mixture was added with ethyl acetate (90 ml), and washed with saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by PTLC (chloroform : methanol = 10: 1) to obtain the title compound (Compound No. V-11, 213 mg).
[Example V-12] Synthesis of 3-{4-cyclohexylmethyloxy-3- [6- (N, N- dimethylcarbamoylmethyloxy) naphthalen-2-yl] phenyl} propionic acid (Compound No.
V-10) According to the procedure described in the synthesis method of Intermediate 9 with the modifications that the reaction was carried out at room temperature for 18 hours and at 60°C for 8 hours, and the purification was performed by PTLC (chloroform : methanol = 10: 1), Compound No. V-11 (213 mg) and 2 N aqueous sodium hydroxide (420, u l) were reacted and treated to obtain the title compound (Compound No. V 12, 115 mg).
[Example V-13] Synthesis of methyl 3- [3- (6-aminonaphthalen-2-yl)-4- cyclopentylmethyloxyphenyl] propionate (Compound No. V-13) According to a known method described in a publication (Anderson, L. C. et al. , J. Am. Chem. Soc, 1943, vol. 65, p. 241), a solution of 2-amino-6- bromonaphthalene (223 mg) obtainable from commercially available 2-brom-6- hydroxynaphthalene (TCI) in anhydrous THF (10 ml) was added with 30% potassium hydride (191 mg, Ald) under ice cooling, and stirred for 1 hour. The reaction mixture was cooled to'78°C under argon gas atmosphere, added dropwise with a 1.7 M solution of t-butyllithium in pentane (1.88 ml) over 10 minutes, and stirred for 30 minutes. This reaction mixture was added dropwise with (iPrO) 3B (0.92 ml) over 10 minutes, stirred for 30 minutes, then warmed to room temperature, and further stirred for 3 hours. The reaction mixture was added with water (3 ml) and 0.5 M aqueous sulfuric acid (4 ml), and extracted with diethyl ether (100 ml x 3). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude 6- amino-2-naphthaleneboronic acid (402 mg). A solution of this substance in ethanol (0.5 ml), Compound No. A-1 (119 mg), 2 M aqueous sodium carbonate (1.5 ml) and (Ph3P) 4Pd (61 mg) were reacted and treated according to the procedure described in the synthesis method of Compound No. V 3 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 4: 1) to obtain the title compound (Compound No. V-13,129 mg).
Example V-14] Synthesis of 3- [3- (6-aminonaphthalen-2-yl)-4-cyclopentylmethyloxyphenyl] propionic acid (Compound No. V-14) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 14 hours, Compound No. V-13 (120 mg) and 2 N aqueous sodium hydroxide (1.75 ml) were reacted and treated to obtain the title compound (Compound No. V-14, 89 mg).
[Example V-16] Synthesis of methyl 3- [3- ({6- [2- (acetyloxy) acetylamino) naphthalen-2-yl}-4- cyclopentylmethyloxyphenyl) propionate (Intermediate 65) A solution of Compound No. V-13 (151 mg) in dichloromethane (4 ml) was added with N-methylmorpholine (50 g 1), and then added with acetyloxyacetyl chloride (48.3 u 1) under ice cooling. The reaction mixture was stirred for 10 minutes, then warmed to room temperature, and further stirred for 4 hours. The reaction mixture was poured into aqueous sodium hydrogencarbonate (100 ml), and ethyl acetate (150 ml) was added for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by PTLC (hexane : ethyl acetate = 1: 1) to obtain the title compound (Intermediate 88,136 mg).
Synthesis of 3- (4-cyclopentylmethyloxy-3-{6- [2- (hydroxyacetyl) amino] naphthalen-2- yl} phenyl) propionic acid (Compound No. V-16) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out at room temperature for 5 hours and at 60°C for 1 hour, Intermediate 65 (135 mg) and 2 N aqueous sodium hydroxide (1.12 ml) were reacted and treated to obtain the title compound (Compound No. V-16,102 mg).
(Example V-18] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (6- methylsulfonylaminonaphthalen-2-yl) phenyl] propionate (Compound No. V-18) A solution of Compound No. V-13 (149.1 mg) in 1,2-dichloroethane (5 ml) was added successively with pyridine (500, u 1) and methanesulfonyl chloride (62 , u 1) under ice cooling, stirred for 1.5 hours, then warmed to room temperature, and stirred for 12 hours. The reaction mixture was added with water (30 ml) and ethyl acetate (90 ml) for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by PTLC (hexane : ethyl acetate = 2: 1) to obtain the title compound (Compound No. V-18, 126 mg).
[Example V-19] Synthesis of 3- [4-cyclopentylmethyloxy-3- (6-methylsulfonylaminonaphthalen-2- yl) phenyl] propionic acid (Compound No. V-19) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out at room temperature for 3 hours and at 60°C for 1 hour, Compound No. V-18 (129 mg) and 2 N aqueous sodium hydroxide (535 A 1) were reacted and treated to obtain the title compound (Compound No. V-19,98 mg).
[Example V-20] Synthesis of methyl 3- {4-cyclopentylmethyloxy-3- [6- (N, N- dimethylsulfamoylamino) naphthalen-2-yl] phenyl} propionate (Compound No. V-20) A solution of Compound No. V-13 (165 mg) in pyridine (5 ml) was added successively with 4-dimethylaminopyridine (104 mg, TCI) and dimethylsulfamoyl chloride (520 u 1, TCI), stirred for 5 days, and then further stirred at 50°C for 4 hours. The reaction mixture was added with water (30 ml) and ethyl acetate (90 ml) ) for extraction. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 6 : 1) to obtain the title compound (Compound No. V-20, 125 mg).
[Example V-21] Synthesis of 3-f4-cyclopentylmethyloxy-3- [6- (N, N- dimethylsulfamoylamino) naphthalen-2-yl] phenyl} propionic acid (Compound No. V- 21) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1.5 hours, Compound No. V-20 (118 mg) and 2 N aqueous sodium hydroxide (460 u 1) were reacted and treated to obtain the title compound (Compound No. V 21, 87 mg).
[Example V-22] Synthesis of 2-bromo-6-sulfamoylaminonaphthalene (Intermediate 66) A solution of chlorosulfonyl isoeyanate (870, u 1, WAKO) in benzene (10 ml) was added dropwise with formic acid (377 u 1, WAKO) under ice cooling, warmed to room temperature, stirred and for 19. 5 hours, then warmed to 40°C, and further stirred for 4 hours. The reaction mixture was added dropwise with a solution of 2- amino-6-bromonaphthalene (443 mg) in benzene (5 ml) under ice cooling, warmed to room temperature, and stirred 21.5 hours. The reaction mixture was filtered to obtain solid, and the solid was added with ethyl acetate, mixed and filtered again.
The solvent of the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 2 : 1) to obtain the title compound (Intermediate 66,158 mg).
Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (6-sulfamoylaminonaphthalen-2- yl) phenyl propionate (Compound No. V-22) According to a procedure described in literature (Miyaura, N. et al., Tetrahedron. Lett. , 1997, p. 3447), Compound No. A-1 (209 mg), bis (pinacolate) diboron (177 mg, Ald), [1, 1'- bis (diphenylphosphono) ferrocene] palladium (II) dichloride (hereinafter abbreviated as"PdCl2 (dppf)", 28 mg, TCI) and potassium acetate (182.3 mg, Ald) were added to DMF (6 ml), and heated to 80°C with stirring under argon gas atmosphere for 5 hours. The reaction mixture was cooled to room temperature, then added with Intermediate 91 (130 mg), PdCl2 (dppf) (30 mg) and 2 M aqueous sodium carbonate (0.9 ml), and heated to 80°C for 21 hours with stirring under argon gas atmosphere.
The reaction mixture was added with ethyl acetate (100 ml), washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 3 : 1) to obtain the title compound (Compound No. V-22, 46 mg).
[Example V-23] Synthesis of 3- [4-cyclopentylmethyloxy-3- (6-sulfamoylaminonaphthalen-2- yl) phenyl] propionic acid (Compound No. V-23) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 24 hours, Compound No. V-22 (41 mg) and 2 N aqueous sodium hydroxide (340, u 1) were reacted and treated to obtain the title compound (Compound No. V-23, 22 mg).
[Example V-27] Synthesis of methyl 3- [4-cyclopentyloxy-3- (lH-indol-5-yl) phenyl] propionate (Compound No. V-27) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out at 80°C for 5 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 5 : 1), Compound No. A-5 (367 mg), 5-indoleboronic acid (310 mg, Frontier), 2 M aqueous sodium carbonate (0.9 ml) and (PhsP) 4Pd (132 mg) were reacted and treated to obtain the title compound (Compound No. V 27, 340 mg).
Example V-28] Synthesis of 3- [4-cyclopentyloxy-3- (lH-indol-5-yl) phenyl] propionic acid (Compound No. V-28) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. V-27 (330 mg) and 2 N aqueous sodium hydroxide (1.40 ml) were reacted and treated to obtain the title compound (Compound No. V-28, 310 mg).
[Example V-29] Synthesis of methyl 3- [4-cyclopentyloxy-3- (1-methyl-lH-indol-5- yl) phenyl] propionate (Compound No. V-29) A solution of Compound No. V-27 (123 mg) in DMF (5 ml) was added with 60% sodium hydride (19 mg) under ice cooling, and stirred for 10 minutes. The reaction mixture was added dropwise with methyl iodide (100 u 1), stirred for 10 minutes, then warmed to room temperature, and further stirred for 1 hour. The reaction mixture was poured into ice water, and ethyl acetate (100 ml) was added for extraction. The organic layer was successively washed with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by flash column chromatography (hexane : ethyl acetate = 8 : 1) to obtain the title compound (Compound No. V-29, 126 mg).
[Example V-30] Synthesis of 3- [4-cyclopentyloxy-3- (1-methyl-lH-indol-5-yl) phenyl] propionic acid (Compound No. V-30) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1 hour, Compound No.
V-29 (123 mg) and 2 N aqueous sodium hydroxide (330 g 1) were reacted and treated to obtain the title compound (Compound No. V-30, 110 mg).
[Example V-31] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (lH-indol-4-yl) phenyl propionate (Compound No. V-31) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 21 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 6: 1), Compound No. A-1 (200 mg), 4-indoleboronic acid (170 mg) obtainable from 4-bromoindole (TCI) according to a known method described in a publication (Doll, M. et al. , J. Org. Chem, 1999, vol. 64, p. 1372), 2 M aqueous sodium carbonate (550, u 1) and (Ph3P) 4Pd (60 mg) were reacted and treated to obtain the title compound (Compound No. V-31,214 mg).
[Example V-32] Synthesis of 3- [4-cyclopentylmethyloxy-3- (lH-indol-4-yl) phenyl] propionic acid (Compound No. V-32) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1 hour, Compound No.
V-31 (210 mg) and 2 N aqueous sodium hydroxide (0.60 ml) were reacted and treated to obtain the title compound (Compound No. V 32, 173 mg).
[Example V-33] Synthesis of 4-bromo-1-methyl-lH-indole (Intermediate 67) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 30 minutes, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 10: 1), 4-bromoindole (5 g), 60% sodium hydride (1.14 g) and methyl iodide (3.18 ml, TCI) were reacted and treated to obtain the title compound (Intermediate 67,4. 95 g).
Synthesis of 1-methyl-lH-indole-4-boronic acid (Intermediate 68) A solution of Intermediate 67 (4.90 g) in anhydrous THF (30 ml) was cooled to-78°C under argon gas atmosphere, then added dropwise with a 1.62 M solution of t-butyllithium in pentane (28. 8 ml) over 30 minutes, and stirred for 30 minutes.
This reaction mixture was added dropwise with (iPrO) 3B (10.77 ml) over 10 minutes, stirred for 1 hour, then warmed to room temperature, and further stirred for 2.5 hours. The reaction mixture was poured into 1.2 N aqueous phosphoric acid (250 ml) containing ice, and extracted with diethyl ether (200 ml x 3). The organic layer was extracted with 0.4 N aqueous sodium hydroxide (150 ml x 3), and the aqueous layer was made acidic with 5 N hydrochloric acid under ice cooling, and extracted with diethyl ether (200 ml x 3) again. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was washed with hexane to obtain the title compound (Intermediate 68,3. 17 g).
Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (1-methyl-lH-indol-4- yl) phenyl] propionate (Compound No. V-33) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 18 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 9: 1), Compound No. A-1 (200 mg), Intermediate 68 (185 mg), 2 M aqueous sodium carbonate (550, u 1) and (Ph3P) 4Pd (60 mg) were reacted and treated to obtain the title compound (Compound No. V-33, 208 mg).
[Example V-34] Synthesis of 3- [4-cyclopentylmethyloxy-3- (1-methyl-lH-indol-4-yl) pheny ] propionic acid (Compound No. V-34) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. V-33 (200 mg) and 2 N aqueous sodium hydroxide (0.60 ml) were reacted and treated to obtain the title compound (Compound No. V-34, 182 mg).
Example V-43] Synthesis of 3-{4-cyclopentylmethyloxy-3- [1-(2-hydroxyethyl)-lH-indol-5- yl] phenyl} propionic acid (Compound No. V-43) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 1.5 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 8 : 1), Compound No. V-27 (144mg), 60% sodium hydride (38 mg) and ethyl bromoacetate (160, u 1, TCI) were reacted and treated to obtain an oily substance.
This substance was reacted with 2 N aqueous sodium hydroxide (300 job 1) and treated according to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 1 hour to obtain the title compound (Compound No. V-43, 36 mg).
[Example V-44] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (3-formyl-lH-indol-5- yl) phenyl] propionate (Compound No. V-44) A solution of Compound No. V-27 (75 mg) in DMF (6 ml) was added dropwise with phosphoryl chloride (30 ju 1, TCI) under ice cooling, stirring for 1 hour, then warmed to 35°C, and further stirred for 1 hour. The reaction mixture was added with 1 N aqueous sodium hydroxide (3 ml) containing ice, and extracted with ethyl acetate (90 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 5 : 1) to obtain the title compound (Compound No. V-44, 86 mg).
[Example V-45] Synthesis of 3- [4-cyclopentylmethyloxy-3- (3-formyl-lH-indol-5-yl) phenyl] propionic acid (Compound No. V-45) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. V-44 (86 mg) and 2 N aqueous sodium hydroxide (110, u 1) were reacted and treated to obtain the title compound (Compound No. V-45, 60 mg).
[Example V-47] Synthesis of methyl 3- [3- (3-acetyl-lH-indol-5-yl)-4- cyclopentylmethyloxyphenyl] propionate (Compound No. V-47) A solution of Compound No. V-27 (98 mg) in methylene chloride (2 ml) was added with aluminum chloride (81 mg, Ald) and acetyl chloride (60, u 1), and stirred for 4 hours. The reaction mixture was added with 1 N hydrochloric acid (2 ml), and extracted with methylene chloride (60 ml). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 4 : 1) to obtain the title compound (Compound No. V-47, 47 mg).
[Example V-48] Synthesis of 3- [3- (3-acetyl-lH-indol-5-yl)-4-cyclop entylmethyloxyphenyl] propionic acid (Compound No. V-48) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 4 hours, Compound No. V-47 (45 mg) and 2 N aqueous sodium hydroxide (110, u 1) were reacted and treated to obtain the title compound (Compound No. V-48, 44 mg).
[Example V-50] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (3-methyl-lH-indol-5- yl) phenyl] propionate (Compound No. V-50) According to the procedure described in the synthesis method of Intermediate 95 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 4: 1), 5-bromo-3-methylindole (1.63 g) obtainable from 5- bromoindole (TCI) by a known method described in a publication (Wayland, E. N. , J.
Org. Chem, 1967, vol. 32, p. 828) was reacted with 30% potassium hydride (1.08 g), a 1.7 M solution of t-butyllithium in pentane (9.7 ml) and (iPrO) 3B (3.75 ml) and treated to obtain crude 3-methyl-5-indoleboronic acid. This compound was reacted with Compound No. A-1 (803 mg), 2 M aqueous sodium carbonate (2 ml) and (PhsP) 4Pd (241 mg) and treated to obtain the title compound (Compound No. V-50, 552 mg).
[Example V-51] Synthesis of 3- [4-cyclopentylmethyloxy-3- (3-methyl-1H-indol-5-yl) phenyl] propionic acid (Compound No. V-51) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. V-50 (130 mg) and 2 N aqueous sodium hydroxide (370, u 1) were reacted and treated to obtain the title compound (Compound No. V-51,127 mg).
[Example V-54] Synthesis of 4-bromo-lH-indazole (Intermediate 69) According to a known method described in a publication (Schumann, P. et al. , Bioorg. Med. Chem. Lett. , 2001, vol. 11, p. 1153), the title compound (Intermediate 69,1. 68 g) was obtained from commercially available 3- bromotoluidine (4.51 g, Ald).
Synthesis of methyl 3- [4-cycloperityloxy-3- (lH-indazol-4-yl) phenyl] propionate (Compound No. V-54) According to the procedure described in the synthesis method of Compound No. V-22 provided that the purification was performed by flash column chromatography (hexane : ethyl acetate = 2: 1), Compound No. A-5 (328 mg), bis (pinacolate) diboron (281 mg), PdCl2 (dppf) (61 mg) and potassium acetate (303 mg) were reacted at 80°C for 4 hours, and then this reaction mixture was added with Intermediate 105 (161 mg), PdCl2 (dppf) (64 mg) and 2 M aqueous sodium carbonate (1.5 ml), reacted at 80°C for 9 hours and treated to obtain the title compound (Compound No. V-54, 111 mg).
[Example V-55] Synthesis of 3- [4-cyclopentyloxy-3- (lH-indazol-4-yl) phenyl] propionic acid (Compound No. V-55) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. V-54 (108 mg) and 2 N aqueous sodium hydroxide (400 g 1) were reacted and treated to obtain the title compound (Compound No. V-55, 99 mg).
[Example V-57] Synthesis of 4- (4,4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-2-methylnitrobenzene (Intermediate 70) According to the procedure described in the synthesis method of Compound No. V-22, 5-bromo-2-nitrotoluene (4.30 g) synthesized by nitrating 3-bromotoluene (WAKO) by a known method, bis (pinacolate) diboron (5.59 g), PdCl2 (dppf) (440 mg) and potassium acetate (6.09 g) were heated with stirring at 80°C for 3 hours under argon gas atmosphere. The reaction mixture was added with ethyl acetate (300 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane: ethyl acetate = 8: 1) to obtain the title compound (Intermediate 70,4. 21 g).
Synthesis of 4- (4,4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-2-methylaniline (Intermediate 71) According to the procedure described in the synthesis method of Compound No. Q-2 with the modification that the reaction was carried out for 30 minutes, Intermediate 70 (4.20 g) and platinum oxide (50 mg) were added, then reacted and treated under hydrogen atmosphere to obtain the title compound (Intermediate 71, 2. 81 g).
Synthesis of methyl 3- (4'-amino-6-cyclop entyloxy-3'-methlbiphenyl-3-yl) propionate (Intermediate 72) According to the procedure described in the synthesis method of Compound No. C-1 with the modifications that the reaction was carried out for 15.5 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 6: 1), Compound No. A-5 (701mg), Intermediate 71 (604mg), 2 M aqueous sodium carbonate (1. 8ml), and (Ph3P) 4Pd (182mg) were reacted and treated to obtain the title compound (Intermediate 72,762 mg).
Synthesis of methyl 3- [4-cyclopentyloxy-3- (lH-indazol-5-yl) phenyl] propionate (Compound No. V-57) A solution of Intermediate 72 (760 mg) in acetic acid (4 ml) was added with an aqueous solution (0.7 ml) of sodium nitrite (156 mg) under ice cooling, and stirred for 30 minutes. This reaction mixture was added with urea (350 mg), warmed to room temperature, stirred for 30 minutes, then added with toluene (8 ml) and water (4 ml), and further stirred for 60 hours. The reaction mixture was extracted with toluene (50 ml x 2). The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 6: 1) to obtain the title compound (Compound No. V 57, 411 mg).
[Example V-58] Synthesis of 3- [4-cyclopentyloxy-3- (lH-indazol-5-yl) phenyl] propionic acid (Compound No. V-58) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2.5 hours, Compound No. V 57 (86 mg) and 2 N aqueous sodium hydroxide (250, u là were reacted and treated to obtain the title compound (Compound No. V 58, 82 mg).
[Example V-66] Synthesis of 5-bromo-3-methyl-lH-indazole (Intermediate 73) According to the procedure described in the synthesis method of Compound No. V-57 provided that the reaction was carried out for 121 hours, 4-bromo-2- ethylaniline (5.01 g, LANC) and sodium nitrite (1.918 g) were reacted and treated to obtain the title compound (Intermediate 73,3. 30 g).
Synthesis of methyl 3- [4-cyclopentyloxy-3- (3-methyl-lH-indazol-5- yl) phenyl] propionate (Compound No. V-66) According to the procedure described in the synthesis method of Compound No. V-22 provided that the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 5: 2), Compound No. A-5 (434 mg), bis (pinacolate) diboron (367 mg), PdCl2 (dppf) (101 mg), and potassium acetate (339 mg) were reacted at 80°C for 4 hours, and then this reaction mixture was added with Intermediate 108 (273 mg), PdCl2 (dppf (104 mg) and 2 M aqueous sodium carbonate (1.1 ml), reacted at 80°C for 18 hours and treated to obtain the title compound (Compound No. V-66, 98 mg).
[Example V-67] Synthesis of 3- [4-cyclopentyloxy-3- (3-methyl-lH-indazol-5-yl) phenyllpropionic acid (Compound No. V-67) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No V-66 (97 mg) and 2 N aqueous sodium hydroxide (400, u 1) were reacted and treated to obtain the title compound (Compound No. V-67, 54 mg).
[Example V-68] Synthesis of methyl 3- [4-cyclopentyloxy-3- (1, 3-dimethyl-lH-indazol-5- yl) phenyl] propionate (Compound No. V-68) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 16 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 3:1), Compound No. V-66 (112 mg), 60% sodium hydride (24 mg) and methyl iodide (95 u 1) were reacted and treated to obtain the title compound (Intermediate 110,45 mg).
[Example V-69] Synthesis of 3- [4-cyclopentyloxy-3- (1, 3-dimethyl-lH-indazol-5-yl) phenyl] propionic acid (Compound No. V-69) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. V-68 (45 mg) and 2 N aqueous sodium hydroxide (120 1) were reacted and treated to obtain the title compound (Compound No. V-69, 42 mg).
[Example V-73] Synthesis of methyl 3- [3- (benzo [b] thiophen-5-yl)-4- cyclopentylmethyloxyphenyl] propionate (Compound No. V-73) According to the procedure described in the synthesis method of Compound No. V-22 provided that the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 10 : 1), Compound No. A-1 (371 mg), bis (pinacolate) diboron (294 mg), PdCI$ (dppf) (67 mg) and potassium acetate (308 mg) were reacted at 80°C for 10 hours, and then this reaction mixture was added with 5-bromobenzo [b] thiophene (301.4 mg) obtainable from 4-bromothiophenol (TCI) by a known method described in a publication (Seed, A. J. , J. Mater. Chem., 2000, vol. 10, p. 2069), PdCl2 (dppf) (65 mg) and 2 M aqueous sodium carbonate (0.9 ml), reacted at 80°C for 16 hours and treated to obtain the title compound (Compound No. V-73,97 mg).
[Example V-74] Synthesis of 3- [3- (benzo [b] thiophen-5-yl)-4-cyclopentylmethyloxyphenyl] propionic acid (Compound No. V-74) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. V-73 (95 mg) and 2 N aqueous sodium hydroxide (250, u 1) were reacted and treated to obtain the title compound (Compound No. V 74, 93 mg).
[Example V-77] Synthesis of (3-bromophenyl) thiourea (Intermediate 74) A solution of 3-bromoaniline (10.89 ml, TCI) in 20% aqueous hydrochloric acid (18. 2 ml) was added with ammonium thiocyanate (8. 02 g, WAKO) and sodium hydrogensulfite (701 mg, WAKO), and stirred at 100°C for 22 hours. The reaction mixture was added with chloroform (20 ml) for extraction, and the organic layer was dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 2 : 1) to obtain the title compound (Intermediate 74,4. 45 g).
Synthesis of 2-amino-5-bromobenzothiazole (Intermediate 75) A solution of Intermediate 74 (1.29 g) in chloroform (12 ml) was added dropwise with a solution of bromine (272 u 1, WAKO) in chloroform (1.5 ml), refluxed by heating for 2.5 hours, and stirred at room temperature for 16 hours.
The reaction mixture was concentrated under reduced pressure, neutralized with 5% aqueous ammonia, and then added with water (50 ml) and methylene chloride (150 ml) for extraction. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 2: 1) to obtain the title compound (Intermediate 75,609 mg).
Synthesis of methyl 3- [3- (2-aminobenzothiazol-5-yl)-4- cyclopentylmethyloxyphenyl] propionate (Compound No. V-77) A solution of Intermediate 75 (459.1 mg) in anhydrous THF (30 ml) was added with N, N, N', N'-tetramethylethylenediamine (1.51 ml, WAKO), cooled to-78°C under argon gas atmosphere, then added dropwise with a 1.62 M solution of t- butyllithium in pentane (7.06 ml), and stirred for 30 minutes. The reaction mixture was added dropwise with (iPrO) 3B (2.77 ml), stirred for 30 minutes, then warmed to room temperature, and further stirred for 1.5 hours. The reaction mixture was added with 0.5 M aqueous sulfuric acid (7.5 ml) and extracted with diethyl ether (50 ml x 3). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude 2-amino-5-benzothiazoleboronic acid. This compound was reacted with Compound No. A-1 (344 mg), 2 M aqueous sodium carbonate (4.5 ml) and (Ph3P) 4Pd (179 mg) and treated according to the procedure described in the synthesis method of Compound No. V-3 with the modifications that the reaction was carried out for 12 hours, and the purification was performed by flash column chromatography (hexane : ethyl acetate = 2: 1) to obtain the title compound (Compound No. V-77, 76 mg).
Example V-78] Synthesis of 3- [3- (2-aminobenzothiazol-5-yl)-4- cyclopentylmethyloxyphenyl] propionic acid (Compound No. V-78) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2.5 hours, Compound No. V-77 (77 mg) and 2 N aqueous sodium hydroxide (380, u 1) were reacted and treated to obtain the title compound (Compound No. V 78, 69 mg).
[Example V-791 Synthesis of ethyl 3- [3- (benzothiazol-5-yl)-4- cyclopentylmethyloxyphenyl] propionate (Compound No. V-79) A solution of Compound No. V-77 (215 mg) in acetonitrile (10 ml) was added with 30% aqueous hypophosphorous acid (3 ml, WAKO), cooled to 0°C, added dropwise with an aqueous solution (1 ml) of sodium nitrite (187 mg), stirred for 30 minutes, then warmed to room temperature, and further stirred for 20 hours. The reaction mixture was poured into water (50 ml), neutralized by addition of 2 N aqueous sodium hydroxide, and added with ethyl acetate (90 ml x 3) for extraction.
The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 10: 1) to obtain the title compound (Compound No. V-79,78 mg).
Example V-80] Synthesis of 3- [3- (benzothiazol-5-yl)-4-cyclopentylmethyloxyphenyl] propionic acid (Compound No. V-80) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours, Compound No. V 79 (75 mg) and 2 N aqueous sodium hydroxide (500, c41) were reacted and treated to obtain the title compound (Compound No. V 80, 66 mg).
[Example V-81] Synthesis of methyl 3- [4-cyclopentylmethyloxy-3- (2-methylbenzothiazol-5- yl) phenyl] propionate (Compound No. V-81) According to the procedure described in the synthesis method of Compound No. V-13 with the modifications that the reaction was carried out for 13 hours, and the purification was performed by flash column chromatography (hexane: ethyl acetate = 5: 1), crude 2-methyl-5-benzothiazoleboronic acid prepared from 5-brom- 2-methylbenzothiazole (684 mg, TCI), a 1.7 M solution of t-butyllithium in pentane (7.06 ml) and (iPrO) 3B (3.46 ml), Compound No. A-1 (515 mg), 2 M aqueous sodium carbonate (6.5 ml) and (Ph3P) 4Pd (258 mg) were reacted and treated to obtain the title compound (Compound No. V-81, 240 mg).
[Example V-82] Synthesis of 3- [4-cyclopentylmethyloxy-3- (2-methylbenzothiazol-5- yl) phenyl] propionic acid (Compound No. V-82) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 4 hours, Compound No. V-81 (227 mg) and 2 N aqueous sodium hydroxide (1. 11 ml) were reacted and treated to obtain the title compound (Compound No. V 82, 132 mg).
[Example V-83] Synthesis of ethyl 3-{4-cyclopentylmethyloxy-3-[2-(N, N- dimethylamino) benzothiazol-6-yl] phenyl} propionate (Comp ound No. V-83) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 4 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 7: 1), Compound No. V-77 (155 mg), 60% sodium hydride (16 mg) and methyl iodide (68. 5 u 1) were reacted and treated to obtain the title compound (Compound No. V-83,48 mg).
[Example V-84] Synthesis of 3- {4-cyclopentylmethyloxy-3- [2- (N, N-dimethylamino) benzothiazol-6- yl] phenyl} propionic acid (Compound No. V-84) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 3 hours, Compound No. V-83 (47 mg) and 2 N aqueous sodium hydroxide (200 u 1) were reacted and treated to obtain the title compound (Compound No. V-84, 35 mg).
Example V-88] Synthesis of ethyl 3- [3- (2-bromobenzothiazol-6-yl)-4- cyclohexylmethyloxyphenyl] propionate (Intermediate 76) A solution obtained beforehand by adding t-butyl nitrite (178 u 1, TCI) and copper (I) bromide (241 mg, WAKO) to acetonitrile (10 ml) and mixing them was added dropwise with a solution of Compound No. V-83 (381 mg) in acetonitrile (5 ml) and stirred at room temperature for 1.5 hours. The solvent of the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (Quad, hexane : ethyl acetate = 10 : 1) to obtain the title compound (Intermediate 76,341 mg).
Synthesis of 3- [4-cyclopentylmethyloxy-3- (2-methoxybenzothiazol-6- yl) phenyllpropionic acid (Compound No. V-88) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 18 hours, Intermediate 76 (169 mg) and 2 N aqueous sodium hydroxide (500, u 1) were reacted and treated to obtain the title compound (Compound No. V-88, 114 mg).
[Example V-89] Synthesis of 3- [4-cyclopentylmethyloxy-3- (2-oxo-2, 3-dihydrobenzothiazol-6- yl) phenyl] propionic acid (Compound No. V-64) A solution of Intermediate 76 (202 mg) in ethanol (8 ml) was added with 5 N aqueous hydrochloric acid (1.5 ml), and stirred at 80°C for 18.5 hours. The reaction mixture was concentrated under reduced pressure, and added with water (20 ml) and ethyl acetate (80 ml) for extraction. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was added with 2 N aqueous sodium hydroxide (1.0 ml), reacted and treated according to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2 hours to obtain the title compound (Compound No. V 89, 250 mg).
[Example V-91] Synthesis of 3- [4-cyclopentylmethyloxy-3- (2-thioxo-2, 3-dihydrobenzothiazol-6- yl) phenyl] propionic acid (Compound No. V-91) A solution obtained beforehand by adding thiourea (52 mg, WAKO) to 1 M sulfuric acid (5 ml) and mixing them was added with a solution of Intermediate 76 (101 mg) in acetonitrile (5 ml), and stirred at 90°C for 20 hours. The reaction mixture was poured into water (20 ml), neutralized by addition of 1 N aqueous sodium hydroxide under ice cooling, and then extracted with ethyl acetate (80 ml x 3). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, methylene chloride : ethanol = 30 : 1) to obtain the title compound (Compound No. V-91,46 mg).
Synthesis examples for compounds used for preparation of the compounds mentioned in the examples are shown below.
Syntheses of 4-bromo-1-methyl-lH-indazole (Intermediate 77) and 4-bromo-2- methyl-2H-indazole (Intermediate 78) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 8 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 5: 1), Intermediate 69 (600 mg), 60% sodium hydride (191 mg), and methyl iodide (379 su 1) were reacted and treated to obtain the title compounds (Intermediate 119,432mg and Intermediate 120,164 mg).
Synthesis of 5-bromo-lH-indazole (Intermediate 79) The title compound (Intermediate 121,0. 91 g) was obtained from commercially available 4-bromotoluidine (3.33 g, Ald) by a method known from the aforementioned literature (Bioorg. Med. Chem. Lett. , 2001, vol. 11, p. 1153).
Syntheses of 5-bromo-1-methyl-lH-indazole (Intermediate 80) and 5-bromo-2- methyl-2H-indazole (Intermediate 81) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 4.5 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 5: 1), Intermediate 79 (300 mg), 60% sodium hydride (80 mg), and methyl iodide (161, u 1) were reacted and treated to obtain the title compounds (Intermediate 80, 201mg and Intermediate 81,87 mg).
Synthesis of 1-methyl-lH-indazole-5-boronic acid (Intermediate 82) According to the procedure described in the synthesis method of Compound No. V-3, Intermediate 80 (1.69 g), a 1.6 M solution of n-butyllithium in hexane (7.50 ml) and (iPrO) 3B (3.23 ml) were reacted and treated to obtain the title compound (Intermediate 82,1. 39 g).
Syntheses of 5-bromo-1-ethyl-lH-indazole (Intermediate 83) and 5-bromo-2-ethyl- 2H-indazole (Intermediate 84) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 5: 1), Intermediate 79 (420 mg), 60% sodium hydride (111 mg), and ethyl iodide (375 A 1) were reacted and treated to obtain the title compounds (Intermediate 83,250mg and Intermediate 84,127 mg).
Synthesis of 6-bromo-lH-indazole (Intermediate 85) The title compound was obtained from commercially available 5- bromotoluidine (3.33 g, Ald) by the method known from the aforementioned literature (Bioorg. Med. Chem. Lett. , 2001, vol. 11, p. 1153) to obtain the title compound (Intermediate 85,0. 42 g).
Syntheses of 6-bromo-1-methyl-IH-indazole (Intermediate 86) and 6-bromo-2- methyl-2H-indazole (Intermediate 87) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 2.5 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 5 : 1), Intermediate 85 (277 mg), 60% sodium hydride (86 mg), and methyl iodide (175 u 1) were reacted and treated to obtain the title compounds (Intermediate 86,196 mg and Intermediate 87,89 mg).
Synthesis of 5-bromo-2-t-butylthiobenzaldehyde (Intermediate 88) A solution of 5-bromo-2-fluorobenzaldehyde (4.06 g, Avocado) in 2-propanol (20 ml) was added with 2-methyl-2-propanethiol (2.26 ml, Ald) and potassium carbonate (3.04 g), and heated with stirring for 18 hours. The reaction mixture was cooled to room temperature, then poured into water (50 ml), and extracted with chloroform (75 ml x 3). The organic layer was washed twice with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 20 : 1) to obtain the title compound (Intermediate 88, 754 mg).
Synthesis of 5-bromobenzo [d] isothiazole (Intermediate 89) A solution obtained beforehand by mixing 2 N aqueous sodium hydroxide (2.19 ml) in an aqueous solution (5 ml) of hydroxylamine hydrochloride (308 mg, WAKO) was added dropwise to. a solution of Intermediate 88 (401 mg) in ethanol (5 ml) at room temperature over 15 minutes. The reaction mixture was refluxed by heating for further 2 hours, then cooled to room temperature, poured into water (30 ml), and extracted with ethyl acetate (100 ml x 3). The organic layer was washed successively with aqueous saturated ammonium chloride aqueous, saturated aqueous sodium hydrogencarbonate, and saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was added with polyphosphoric acid (21.4 g), and heated with stirring at 100°C for 2 hours. The reaction mixture was poured into ice water (100 ml), neutralized with 5 N aqueous sodium hydroxide under ice cooling, and then extracted with ethyl acetate (100 ml x 3). The organic layer was washed twice with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 20 : 1) to obtain the title compound (Intermediate 89,143 mg).
Synthesis of 5-bromobenzo [c] isothiazole (Intermediate 90) A solution of methanesulfonamide (5.34 g, TCI) in dehydrated benzene (9 ml) was added with thionyl chloride (6.0 ml) under ice cooling, and refluxed by heating for 24 hours. The reaction mixture was concentrated under reduced pressure, and a solution of the residue in dehydrated benzene (4 ml) was added dropwise to a solution of 4-bromotoluidine (1.49 g) in dehydrated benzene (40 ml) under ice cooling. This mixture was added dropwise with a solution of pyridine (0. 97 ml) in dehydrated benzene (4 ml) under ice cooling, and refluxed by heating for 80 hours under argon gas atmosphere. The reaction mixture was cooled to room temperature, poured into water (100 ml), and extracted with chloroform (100 ml x 3). The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 10 : 1) to obtain the title compound (Intermediate 90,618 mg).
Synthesis of 6-bromoimidazo [1, 2-a] pyridine (Intermediate 91) The title compound (Intermediate 91, 3.36 g) was obtained from commercially available bromoacetaldehyde-diethylacetal (4.7 ml, WAKO) and 2- amino-5-bromopyridine (4. 32 g, Ald) by a known method described in a publication (Yamanaka, M. et al. , Chem. Pharm. Bull. , 1991, vol. 39, p. 1556).
Synthesis of 5-bromo-lH-pyrrolo [2, 3-b] pyridine (Intermediate 92) The title compound (Intermediate 92,182 mg) was obtained from commercially available lH-pyrrolo [2, 3-b] pyridine (1.3 g, TCI) by a known method described in a publication (Mazeas, D. et al, Heterocycles, 1999, vol. 50, p. 1065).
Synthesis of 5-bromo-l-methyl-lH-pyrrolo [2, 3-b] pyridine (Intermediate 93) According to the procedure described in the synthesis method of Compound No. V-29 with the modifications that the reaction was carried out for 2 hours, and the purification was performed by column chromatography (Quad, hexane : ethyl acetate = 15 : 1), Intermediate 92 (98 mg), 60% sodium hydride (33 mg), and methyl iodide (53 u 1) were reacted and treated to obtain the title compound (Intermediate 93, 88 mg).
Synthesis of 6-bromoisoquinoline (Intermediate 94) The title compound (Intermediate 94,1. 46 g) was obtained from commercially available 4-bromobenzaldehyde (15. 0 g, WAKO) by a known method described in a publication (Nerenz, H. et al. , J. Chem. Soc. Perkin Trans. 2,1998, p. 437].
Synthesis of 6-bromo-2H-isoquinolin-1-one (Intermediate 95) A solution of Intermediate 94 (1.04 g) in methylene chloride (3 ml) was added with a solution of 3-chloroperbenzoic acid (2.16 g) in methylene chloride (3 ml), and stirred for 20 hours. The reaction mixture was added with methylene chloride (200 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine.
The organic layer was dried, and then the solvent was evaporated under reduced pressure. A solution of the residue in acetic anhydride (10 ml) was refluxed by heating for 5 hours. The reaction mixture was concentrated under reduced pressure, and then the residue was added with 2.5 N aqueous sodium hydroxide (20 ml), and stirred at 100°C for 1 hour. The reaction mixture was cooled to room temperature, and neutralized with 5 N aqueous hydrochloric acid under ice cooling to obtain the precipitated title compound (Intermediate 95,623 mg).
[Examples V-1 to V-115] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-V-1 to Table-V-3. zx R.-0-Y o---yo O Table-V-1 Exp. RxO Y Zx AR Syn method RTime Mass V-1 cHexMeO Et H V-2 cHexMeO H H V-3 cPenMeO Me V-3 V-4 cPenMeO H H 60H-2-Nap V-4 V-5 cPenMeO Me H 50H-2-Na V-5 V-6 cPenMeO H H 50H-2-Nap V-6 V-7 cPenMeO Me H 70H-2-Nap V-7 V-8 cPenMeO H H 70H-2-Nap V-8 V-9 cPenMeO Me H 60Me-2-Nap V-1 V-10 cPenMeO H H 60Me-2-Nap V-2 C _ V-11 Me H 6 (OCH2CONMe2)-2-Nap V-12 cPenMeO H H 6 (OCHCONMe2)-2-Nap V-12 V-13 cPenMeO Me H 6NH2-2-Nap V-14 cPenMeO H H 6NH2-2-Nap V-14 V-15 cPenMeO H H 6 (NMe2)-2-Nap V-16 cPenMeO H H 6 (NHCOCH2OH)-2-Nap V-16 V-17 cPenMeO H H 6 (NHCO-2-Furan)-2-Nap V-16 C V-18 cPenMeO Me H 6 (NHSO2Me)-2-Nap V-18 V-19 H H 6 (NHSO2Me)-2-Nap V-19 V-20 cPenMeO Me H 6 (NHS02NMe2)-2-Nap V-20 V-21 cPenMeO H H 6 (NHS02NMe2)-2-Nap V-22 cPenMeO Me H 6 (NHS02NH2)-2-Nap V-23 cPenMeO H H 6 (NHS02NH2)-2-Nap V-23 V-24 cPenMeO H H 6 (SO2Me)-2-Nap V-22, V-23 V-25 cPenMeO H 6 (SO2NH2)-2-Nap V-22, V-23 C V-26 cPenMeO H H 6 (SO2NHMe)-2-Nap V-22, V-23 C V-27 cPenO Me H 5-tond V-27 V-28 cPenO H 5-Ind V-29 cPenO Me H 1 V-30 cPenO H H 1 Me-5-Ind V-30 V-31 cPenMeO Me H V-32 cPenMeO H H V-33 cPenMeO Me H 1 Me-4-Ind V-34 cPenMeO H H 1 V-35 cPenMeO H H 6-Ind V-31, V-32 C V-36 cPenMeO H H 1-Me-6-Ind V-34 V-37 cPenMeO H H V-32 A 5. 35 364 (M++1) V-38 cPenMeO H H 1 V-30 V-39 cPenMeO H H V-32 V-40 cPenMeO H H 1 V-30 A 4. 75 363 (M++1) V-41 cPenMeO H H 1 iPr-5-Ind V-29, V-30 C V-42 cPenMeO H H 1 V-30 C V-43 cPenMeO H H 1- ARTable-V-2 V-44 cPenMeO Me H V-45 cPenMeO H H 3CHO-5-Ind V-46 cPenMeO H H 3CHO, 1 V-30 C V-47 cPenMeO Me H 3Ac-5-Ind V-47 V-48 cPenMeO H H 3Ac-5-Ind V-49 cPenMeO H H 3Ac, 1Me-5-Ind V-30 C V-50 cPenMeO Me H 3Me-5-Ind V-51 cPenMeO H H 3Me-5-Ind V-52 cPenMeO H H 1, 3DMe-51nd V-29, V-30 C V-53 cPenMeO H H 1, 2, 3triMe-51nd V-30 C V-54 cPenO Me H 4-1 Hldz V-54 V-55 cPenO H H 4-1 HIdz V-55 V-56 cPenO H H 1 V-30 V-57 cPenO H 5-1 Hldz V-57 V-58 cPenO H H 5-1 HIdz V-58 V-59 cPenO H H 1 V-30 V-60 cPenO V-30 V-61 cPenO H H V-30 V-62 cPenO H H 2Me-5-2HIdz V-30 V-63 cPenMeO H H 6-1 Hldz V-57, V-64 cPenMeO H H 1 V-65 cPenMeO H H 1 V-30 V-66 cPenO Me H 3Me-5-1 V-66 V-67 cPenO H H 3Me-5-1 V-67 V-68 cPenO Me H 1, 3DMe-5-lHIdz V-68 cPenO H H V-69 cPenO H H 3 (CHO)-5-1 V-23 V-70 cPenO H H 3 (CHO), V-23 A 4. 38 365 (M++1) V-71 cPenO H H 30H-5-1 Hldz V-23 V-72 cPenO H H 30H, 1 V-22, V-23 A 3. 71 381 M++1) V-73 cPenMeO Me H 5-BT V-73 V-74 cPenMeO H H 5-BT V-74 V-75 cPenMeO H H 5-BF V-22, V-23 C 378CM+) V-76 cPenMeO H H 2, 3DMe-5-BF V-22, V-23 C V-77 cPenMeO Me H 5-2ABzt V-77 V-78 cPenMeO H H 5-2ABzt V-78 V-79 cPenMeO Et H 5-Bzt V-79 V-80 cPenMeO H H 5-Bzt V-80 V-81 cPenMeO Me H 2Me-5-Bzt V-81 V-82 cPenMeO H H 2Me-5-Bzt V-82 V-83 cPenMeO Et H 2, 2DMe-5-2ABzt V-83 V-84 cPenMeO H H 2, 2DMe-5-2ABzt V-84 V-85 cPenMeO H H 6-2ABzt V-77, V-78 C V-86 cPenMeO H H 6-Bzt V-79, V-80 C V-87 cPenMeO H H 2Me-6-Bzt V-81, V-82 C V-88 cPenMeO H H MeO<g s 4 V-89 cPenMeO H H H H 3CHO-Table-V-3 V-90 cPenMeO H H OtN V-30 C 412 (M++1) edv V-91 cPenMeO H 414 (M++1) N V-92 cPenMeO H H V-29, V-30 C 425 N V-93 cPenO H V-23 B 3. 87 368 (M++1) > V-94 cPenO H H V-23 B 3. 58 368 (M++1) zu V-95 cPenO H H H V-23 A 2. 57 315 (M++1) _ V-96 cPenO H H N V-23 A 3. 84 351 (M++1) H V-97 cPenO H H N-N V-30 A 4. 28 365 (M++1) V-98 cPenMeO H H 3-Qu V-22, V-23 C 376 (M++1) V-99 cPenMeO H H V-100 H H ! V-22, V-23 A 2. 15 452 (M++1) V-101 V-23 A 3. 74 378 (M++1) 0 V-102 cPenMeO H H N V-23 C 378 (M++1) H V-103 cHexMeO Et H V-33 C 406 (M+) V-104 V-34 C 378 (M++1) V-105 cHexMeO Et H 422 (M+) 1 V-106 cHexMeO H H 394 (M+) S V-107 V-23 C 455 (M++1) V-1 07 cHexMeO HNN-- N V-108 cHexMeO H H C5--, V-23 C 495 tv-' V-109 cHexMeO H H V-22, V-23 C 487 (M++1) N V-110 cPenO H H 3 (COOH), lMe-7-lHldz V-23 A V-111 cPenO H H 3 (COOH), 1Me-5-lHldz V-23 A 3. 75 409 (M++1) V-112 cPenO H H 3 (COOH), 2Me-5-2HIdz V-22, V-23 A 3. 96 409 (M V-113 H H 3 (COOH), 2Me-7-2HIdz V-22, V-23 A 3. 80 409 (M++1) V-114 cPenO H H 3 (COOH)-7-lNldz 3. 66 395 (M++1) V-115 H H 3 (CQOH)-5-1 V-23 A 3. 49 395 (M++1) [Examples W-1 to W-25] Synthesis of 6-bromocinnoline (Intermediate 96) The title compound (Intermediate 96,134 mg) was obtained from commercially available 4-bromo-2-iodoaniline (711 mg, Ald) by a method known from literature (Kimball, D. et al., Organic Letter, 2000, p. 3825).
Synthesis of 7-bromoquinazoline (Intermediate 97) The title compound (Intermediate 97,921 mg) was obtained from commercially available quinazoline (2.11 g, WAKO) by a known method described in a publication (Dalby, B. et al. , Synthesis, 2002, p. 83).
Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table-W-1 and Table-W-2. zx Rx--Y Rr \/O Table-W-1 Exp. RxO Y Zx AR Syn LCMS method Mass W-1 cPenMeO H H V-23 C 366 (M++1) H W-2 cPenMeO H H SN N V-23 C 383 (M++1) N N V-23 C 365 (M++1) H W-4 cPenMeO H H Me-< V-23 C 380 (M++1) H W-5 cPenMeO H H o 'V-22, V-23 C 366 (M++1) W-6 cPenMeO H H V-22, V-23 C 380 (M++1) W-7 cPenMeO H V-23 C 381 (M++1) 0 W-8 cPenMeO H H sN V-23 C 398 (M++1) H W-9 cPenMeO H H o>Nw V-23 C 382 (M++1) W-10 H H <o V-23 C 366 (M+1) W-11 cPenMeO H H EN V-23 C 377 (M++1) W-12 cPenO H H V-23 A 3. 97 363 (M++1) W-13 H H N V-23 A 4. 06 363 (M++1) - N, : P 11, W-14 cPenMeO H V-23 C 380 (M++1) H W-15 cPenO H H V-22, V-23 C 355 (M++1) H W-16 cPenMeO H H gX V-23 C 397 (M++1) W-17 cPenMeO H H OtNw V-23 C 381 (M++1) -------------------------------H---------------------------- ------------------ W-18 cPenMeO H cPenMeO V-23 C 380 (M++1) ARTable-W-2 W-19 cPenMeO H H HZN-CN 381 W-20 V-23 C 398 (M++l) H W-21 cPenMeO H H V-22, V-23 C 382 (M++l) H W-22 V-23 C 351 (M++1) I N 353 (M+1) H W-24 cPenO V-23 C 353 (M++l) W-25 H H of H [Example X-1] Synthesis of ethyl 3- [2-cyclopentyloxy-5- (nap hthalen-2-yl) p henyll acrylate (Intermediate 98) According to the procedure described in the synthesis method of Intermediate 7 provided that the reaction was carried out for 1 hour, Compound No.
D-20 (396 mg), ethyl diethylphosphonoacetate (288 u 1), and 60% sodium hydride (59 mg) were reacted and treated to obtain the title compound (Intermediate 98, 428 mg).
Synthesis of ethyl 3- [2-cyclohexylmethyloxy-5- (naphthalen-1-yl) phenyl] propionate (Compound No. X-1) According to the procedure described in the synthesis method of Intermediate B-99 with the modifications that the reaction was carried out at 50°C for 5 hours, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 10: 1), Intermediate 98 (361 mg) and Raney 2800 nickel (380 mg) were reacted and treated to obtain the title compound (Compound No. X-1, 397 mg).
[Example X-2] Synthesis of 3- [2-cyclohexylmethyloxy-5- (naphthalen-l-yl) phenyl] propionic acid (Compound No. X-2) According to the procedure described in the synthesis method of Intermediate 9 provided that the reaction was carried out for 2.5 hours, Compound No. X-1 (390 mg) and 2 N aqueous sodium hydroxide (1. 1 ml) were reacted and treated to obtain the title compound (Compound No. X-2, 338 mg).
[Examples X-1 to X-4] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-X-l. Rx-O s 42< 2) 'I (CH Table-X-1 Exp.'Rx0 positio method Rime Mass X-1 cPenO Et 2 2-Nap X-1 5 X-2 cPenO H 2 2-Nap X-2 5 C X-3 cPenO H 2 1 5 C X-4 cPenO H 2 1 [Reference Examples: Intermediates Aa-1 to Aa-47] Synthesis of methyl 3- [3- (naphthalen-2-yl)-4-trifluoromethanesulfonylphenyl]- propionate (Intermediate Aa-1) A solution of Intermediate 41 (4.34 g) in dehydrated pyridine (120 ml) was added with trifluoromethanesulfonic anhydride (2.6 ml, ALD) under ice cooling, then warmed to room temperature, and stirred for 4 hours. The reaction mixture was concentrated under reduced pressure, and then extracted with ethyl acetate (800 ml). The organic layer was washed successively with 1 N hydrochloric acid, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 6 : 1) to obtain the title compound (Intermediate Aa-1, 4.98 g).
Typical examples of the reaction intermediates including those mentioned above, that can be obtained by reacting and treating corresponding starting compounds according to the synthesis method of Intermediate Aa-1, are shown in Table-Aa-1.
In the column indicated as"Mass"in the table, data of mass spectra measured by fast atom bombardment mass spectrometry (FAB-MS) are shown. ou oW§o F3C Table-Aa-1 Au Exp. AR Mass Exp. AR Mass Ex Aa-1 2-Nap Aa-25 1Me-4-1Hldz Aa-2 (M Aa-26 5-1 Hldz 429 (M Aa-3 1 Me-5-Ind 442 (M Aa-27 1 Aa-4 5-1 Hldz 429 (M Aa-5 1Me-5-1Hldz 443 (M 471 (M Aa-6 5-BF Aa-30 2Me-5-2Hldz Aa-7 3-Qu 440 (M Aa-31 6-1 429 (M Aa-8 1-Nap 443 (M Aa-9 6 (MeO)-2-Nap 469 (M Aa-33 3Me-5-lHldz 443 (M+1) Aa-10 6 (NMe2)-2-Nap Aa-34 1, 3DMe-5-1Hldz l Aa-11 Aa-35 5-BT 445 (M Aa-12 2, 3DMe-5-BF Aa-13 Aa-37 5-2ABzt Aa-14 442 (M 5-Bzt 456 (M v Aa-1 428 (M Aa-39 2Me-5-Bzt Aa-16 Aa-40 2, 2DMe-5-2ABzt Aa-17 428 (M Aa-41 6-2ABzt 461 (M Aa-18 1Me-3-Ind 442 (M++1) Aa-42 6-Bzt Aa-19 Aa-43 2Me-6-Bzt Aa-20 1cPen-5-lnd Aa-44 6-Qu Aa-21 3Me-5-Ind 440 (M++1) Aa-22 1, 3DMe-5Ind 456 (M Aa-46 2-BF 429 (M+1) Aa-23 1, 23triMe-Slnd Aa-47 2-BT 445 (M++1) I Aa-24 4-tHIdz 0+ sOS, O-Me[Example Ca-1] Synthesis of methyl 3- [4- (phenyl)-3- (naphthalen-2-yl) phenyl] propionate (Compound No. Ca-1) Compound No. Aa-1 (138. 4 mg, corresponding to the substance mentioned in the column of SM1 in Table-Ca-1 mentioned later), phenylboronic acid (71.3 mg, corresponding to the substance mentioned in the column of SM 2 mentioned in Table-Ca-1 mentioned later), cesium carbonate (254.9 mg), PdCl2 (dppf) (25.6 mg) were added with toluene (600 sl l), methanol (1.2 ml), and water (1. 2 ml), and stirred at 80°C for 17 hours under nitrogen atmosphere. The reaction mixture was added with ethyl acetate (30 ml), washed successively with water and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 8: 1) to obtain the title compound (Compound No. Ca-1, 140.6 mg).
[Example Ca-2] Synthesis of 3- [4-phenyl-3- (naphthalen-2-yl) phenyl] propionic acid (Compound No.
Ca-2) A solution of Compound Ca-1 (137.7 mg) in methanol (4.0 ml) was added with 2 N aqueous sodium hydroxide (720 u 1), and stirred at 60°C for 16 hours.
The reaction mixture was concentrated under reduced pressure, then made acidic with 5% aqueous hydrochloric acid under ice cooling, and extracted with ethyl acetate (50 ml). The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Compound No. Ca-2,108 mg).
[Examples Ca-1 to Ca-270 and Examples Cb-1 to Cb-95] Typical examples of the compounds of the present invention including those mentioned in the examples described above, that can be obtained by reacting and treating corresponding starting compounds according to the methods described in Examples Ca-1 and Ca-2, are shown in Table-Ca-1 to Table-Ca-5, Table-Cb-1 and Table-Cb-2.
The substances mentioned in the columns of"SM1"in the tables correspond to reaction intermediates, and those mentioned in the columns of"SM2"in the tables correspond to the boronic acid reagent used in Example Ca-1. The boronic acid reagents shown with the symbols of"BRA (number) "mentioned in the columns of"SM2"are those mentioned in Table-Ba-1 and Table-Ba-2. The regents for which cells of the columns of"Manufacturer"in the tables are blank are synthesized according to a method described in ordinary chemical literatures.
Table-Ba-1 Reagen Name of reagent Manufacturer Reagen Name of BRA1 Naphthalene-2-boronic BRA23 Cyclopropyl boronic acid acid BRA2 (1 H-Indol-5-yl) boronic Frontier acid boronic acid BRA3 5-yl) boronic acid 2-boronic acid BRA4 (1-Ethyl-1 Pyridine-4-boronic acid 5-yl) boronic acid BRA5 (1 BRA27 Dibenzofuran-2-boronic boronic acid acid BRA6 (1-Methyl-1H-indazol-BRA28 boronic acid 5-yl) boronic acid BRA7 (1-Ethyl-1 5-yl) boronic acid acid BRA8 (2-Methyl-2H-indazol-BRA30 5-yl) boronic acid acid BRA9 Benzothiazole-6-yl-BRA31 boronic acid 4, 4, 5, 5-tetramethyl- 1, 3, 2-dioxaborolan BRA10 Quinoline-3-boronic acid Frontier BRA32 2-Fluorophenyl boronic acid BRA11 Quinoline-6-yl-4, 4, 5, 5- acid Aid tetramethyl- 1, 3, 2-dioxaborolan BRA12 Isoquinoline-6-yl-BRA34 4-Fluorophenyl boronic acid Aid 4, 4, 5, 5-tetramethyl- 1, 3, 2-dioxaborolan BRA13 Methyl boronic acid Ald boronic acid BRA14 Phenyl boronic acid Aid boronic acid BRA15 boronic Aid BRA37 3-Methoxyphenyl boronic acid Aid acid BRA16 boronic acid acid BRA17 3. 5-Bis (trifluoromethyl) phenyl boronic acid boronic acid BRA18 Benzo [b] furan-2-boronic Ald BRA40 3- acid boronic acid BRA19 4-Methoxypheny boronic Aid BRA41 4- acid boronic acid BRA20 2-Methyipropyl 5, 5-tetramethyl- acid 1, 3, 2-dioxaborolane BRA21 4-(Dimethylamino) 5, 5- boronic acid tetramethyl-1, 3, 2-dioxaborolane BRA22 4-Fluorophenyl boronic 5, 5- acid tetramethyl-1, 3, 2-dioxaborolane reageTable-Ba-2 Reagent Name of reagent of reagent 8RA45 4, 7-Dimethylindan-2~yl~4. boronic acid Ald tetramethvl-1 BRA46 5, 6-Dimethylindan-2-yl-4, 4, 5, 5- BRA68 3-Thienyl boronic Ald tetramethvl-1. BRA47 5-Fluoroindan-2-yl-4, 4, 5, 5-BRA69 tetramethyl-1, 3, 2-dioxaborolane 4, 4, 5, 5-tetramethyl- 1 BRA48 4-Fluoroindan-2-yl-4, Pyridine-3-boronic Ald tetramethvl-1 BRA49 4, 7-Difluoroindan-2-yl-4, 4, 5, 5- 2, 3-Dimethylphenyl tetramethvl-1. acid BRA50 5, 6-Difluoroindan-2-yl-4, 5, 5- 2, 5-Dimethylphenyl _ acid BRA51 4-Chloroindan-2-yl-4, 4, 5, 5-BRA73 tetramethvl-1. acid BRA52 5-Chloroindan-2-yl-4, 5, 5-RA74 tetramethvl-1. acid BRA53 4, 7-Dichloroindan-2-yl-4, BRA75 2, 4-DiChlorophenyl tetramethvl-1 acid BRA54 5, 6-Dichloroindan-2-yl-4, 5, 5- tetrameth 2-dioxaborolane boronic acid BRA55 4, 5, 5- tetramethvl-1. boronic acid BRA56 5-Methoxyindan-2-yi-4, 4, 5, 5- tetrameth boronic acid BRA57 5, 6-Dimethoxyindan-2-yl-BRA79 4 BRA58 acid Aid BRA80 2, 3-Difluorophenyl Ald boronic acid BRA59 2-Methylphenyl boronic acid Aid BRA81 2, 4-Difluorophenyl boronic acid BRA60 boronic acid Aid BRA82 2, 5-Difluorophenyl Aid boronic acid BRA61 boronic acid Ald BRA83 2, 6-Difluorophenyl Aid boronic acid RA62 boronic acid Aid BRA84 3, 4-Difluorophenyl Aid boronic acid BRA63 3, 5-Difluorophenyl Aid boronic acid boronic acid BRA64 boronic acid boronic acid BRA65 BRA87 3- boronic acid Phenyl boronic acid BRA66 BRA88 4-Phenoxy phenyl Ald boronic zx Ou Ru Table-Ca-1 Exp. Rx Y Zx AR SM1 SM2 LCMS method Ca-1 H 2-Nap Aa-1 BRA14 D Ca-2 H 2-Nap Ca-1 Ca-3 H 5-Ind Aa-2 BRA14 Ca-4 H 5-Ind Ca-3-C Ca-5 H 1 Aa-3 BRA14 Ca-6 H 1Me-5-Ind +1) Ca-7 H 5-1 Aa-4 BRA14 Ca-8 H lMe-5-lHldz Aa-5 BRA14 C Ca-9 H H +1) Ca-10 H 5-BF Aa-6 B Ca-ll H 3-Qu Aa-7 BRA14 C +1) Ca-12 H 1-Nap Aa-8 BRAl Ca-13 H 6 (OMe)-2-Nap Aa-9 BRA14 383 Ca-14 H Aa-10 BRA14 C Ca-15 H 4-Ind Aa-11 BRA14 C Ca-16 H 1 BRA14 C +1) Ca-17 H 6-Ind Ca-18 H 1 Me-6-Ind BRA14 C Ca-19 H 2-Ind BRA14 C Ca-20 Ph H H BRA14 C Ca-21 H 3-lnd Ca-22 H 1Me-3-Ind BRA14 C 356 (M Ca-23 Ph H liPr-5-Ind Ca-24 Ph Aa-20 BRA14 C Ca-25 H 3Me-5-Ind Aa-21 BRA14 C Ca-26 Aa-22 BRA14 C 370 Ca-27 H 1, 2. 3triMe-5Ind Ca-28 H 4-lHldz Aa-24 BRA14 C Ca-29 H H Aa-25 BRA14 C Ca-30 H 5-1 Aa-26 BRA14 C Ca-31 H H Aa-27 BRA14 C Ca-32 H H Aa-28 BRA14 C Ca-33 H 1Pr-5-1HMz +l) Ca-34 H 2Me-5-2HIdz Aa-30 BRA14 D Ca-35 H 6-lHldz Aa-31 BRA14 C Ca-36 Ph H H Aa-32 BRA14 C Ca-37 H 3Me-5-lHldz Aa-33 BRA14 C Ca-38 H 1, 3DMe-5-lHldz Aa-34 BRA14 C371 Ca-39 H 5-BT Aa-35 BRA14 C Ca-40 H 2, 3DMe-5-BF Aa-36 BRA14 Ca-41 Ph 5-2ABzt Aa-37 BRA14 C Ca-42 H 5-Bzt Aa-38 BRA14 C Ca-43 H 2Me-5-Bzt Aa-39 BRAl Ca-44 H 2, 2DMe-5-2ABzt Aa-40 BRA14 C Ca-45 Ph H 6-2ABzt Aa-41 BRA14 C Ca-46 H 6-Bzt Aa-42 B Ca-47 H 2Me-6-Bzt Aa-43 BRA14 C +1) Ca-48 H 6-Qu Aa-44 BRA14 +1) Ca-49 H 6-IQ Aa-45 B Ca-50 H H Manufacture Reagent NameTable-Ca-2 Exp. Rx Y Zx AR SM1 SM2 LCMS method RTime Mass Ca-51 H 2-BT Aa-47 BRA14 C Ca-52 4MeOPh H H Aa-1 BRA19 C Ca-53 4MeOPh H H 1Me-5-Ind Aa-3 BRA19 C Ca-54 4MeOPh H H _ Aa-4 BRA19 C Ca-55 4MeOPh H H Aa-5 BRA19 Ca-56 4MeOPh H H 3-Qu Aa-7 BRA19 C Ca-57 4MeOPh H H 1 Aa-28 BRA19 Ca-58 3MeOPh H H 5-Ind Aa-2 BRA37 372 Ca-59 3MeOPh H H 1Me-5-Ind Aa-3 BRA37 386 Ca-60 3MeOPh H H 5-1 Aa-4 BRA37 C Ca-61 3MeOPh H H 1 Aa-5 BRA37 C Ca-62 3MeOPh H H 3-Qu Aa-7 BRA37 384 Ca-63 3MeOPh H H 1 Aa-28 BRA37 401 Ca-64 2MeOPh H H 2-Nap Aa-1 BRA38 C Ca-65 2MeOPh H. H 5-Ind Aa-2 BRA38 C Ca-66 2MeOPh H H 1Me-5-Ind Aa-3 BRA38 Ca-67 2MeOPh H H 5-1 Aa-4 BRA38 C Ca-68 2MeOPh H H 1 Aa-5 BRA38 C Ca-69 2MeOPh H H 5-Bzt Aa-38 BRA38 C Ca-70 2MeOPh H H 3-Qu Aa-7 BRA38 C Ca-71 2MeOPh H H lEt-5-lHldz Aa-28 BRA38 C Ca-72 2MePh H H 2-Nap Aa-1 BRA59 C Ca-73 2MePh H H 5-lnd Ca-74 2MePh H H 1 Aa-3 BRA59 C Ca-75 2MePh H H 5-lHldz Aa-4 BRA59 C Ca-76 2MePh H H 1 Aa-5 BRA59 C Ca-77 2MePh H H 5-Bzt Aa-38 B Ca-78 3MePh H H 2-Nap Aa-1 BRA60 C Ca-79 3MePh H H 5-Ind Aa-2 BRA60 C Ca-80 3MePh H H 5-1 Hldz Aa-4 BRA60 C Ca-81 3MePh H H 1 Aa-5 BRA60 C 371 (M Ca-82 3MePh H H 5-Bzt Aa-38 BRA60 C Ca-83 3MePh H H 1 Aa-28 BRA60 Ca-84 4MePh H H 2-Nap Aa-1 BRA29 C Ca-85 4MePh H H 5-Ind Aa-2 BRA29 C 356 Ca-86 4MePh H H 1Me-5-Ind Aa-3 BRA29 C Ca-87 4MePh H H 5-1 Aa-4 BRA29 C Ca-88 4MePh H H 1 Aa-5 BRA29 C Ca-89 4MePh H H 5-Bzt Aa-38 BRA29 C Ca-90 4MePh H H 3-Qu Aa-7 BRA29 C Ca-91 4MePh H H 1 Aa-28 BRA29 C Ca-92 23DMePh H 5-Ind Aa-2 BRA71 C Ca-93 2, 3DMePh H H 1Me-5-Ind Aa-3 BRA71 C Ca-94 2, 3DMePh H H 5-1 Hldz Aa-4 BRA7 Ca-95 2, 3DMePh H H 1 Aa-5 BRA71 C Ca-96 2, 3DMePh H H 1Et-5-1HIdz Aa-28 BRA71 Ca-97 2, H H 2-Nap Aa-1 BRA72 C Ca-98 2, 5DMePh H H 1Me-5-Ind Aa-3 BRA72 Ca-99 2, 5DMePh H H 5-1 Aa-4 BRA72 C371 a Ca-100 5DMePh H H 1 BRA72 C Ca-101 2, 5DMePh H H 1 Aa-28 BRA72 C Ca-102 3, 5DMePh H H 2-Nap Aa-1 BRA73 C Ca-l 5DMePh H H 1Me-5-Ind Aa-3 BRA73 C Ca-104 3, 5DMePh H H Aa-5 B Ca-105 2-Nap Aa-l Ph HTable-Ca-3 Exp. Rx Y Zx AR SM1 SM2 method Mass Ca-106 H H 5-lnd Ca-107 H H 1 Aa-5 BRA39 C Ca-108 H H 5-Bzt Aa-38 BRA39 C Ca-109 H H 3-Qu Aa-7 BRA39 C Ca-110 H H 1 Aa-28 BRA39 C Ca-111 3CF3Ph H H 2-Nap Aa-1 BRA40 C Ca-112 H H 5-land Aa-2 BRA40 C Ca-113 H H 1 Aa-3 BRA40 Ca-114 H H 1Me-5-lHldz Aa-5 BRA40 Ca-115 H H 5-Bzt Aa-38 BRA40 C Ca-116 H H 3-Qu Aa-7 BRA40 C Ca-117 H H 5-Ind Aa-2 BRA41 C Ca-118 H H 5-1 Hldz Aa-4 BRA41 C Ca-119 4CF3Ph H H 1 Aa-5 BRA41 Ca-120 H H 5-Bzt Aa-38 BRA41 C Ca-121 4CF3Ph H H 3-Qu Aa-7 BRA41 C Ca-122 H H 1 Aa-28 BRA41 C Ca-123 H H 5-Ind Aa-2 BRA61 C Ca-124 H H 5-lHldz Ca-125 H H 1 Aa-5 BRA61 Ca-126 H H 3-Qu Aa-7 BRA61 Ca-127 H H 2-Nap Aa-1 BRA62 C Ca-128 Aa-3 BRA62 C +1) Ca-129 H H 5-1Hldz Aa-4 BRA62 C Ca-1 H H lMe-5-lHldz Aa-5 BRA62 Ca-131 H H 5-Bzt Aa-38 BRA62 C Ca-132 H H 5-Ind Aa-2 BRA30 C Ca-133 H H 1Me-5-Ind Aa-3 BRA30 C Ca-134 H H 1 BRA30 C Ca-135 H H 5-Bzt Aa-38 BRA30 C Ca-136 H H 5-Ind Aa-2 BRA74 C Ca-137 H H 1Me-5-Ind Aa-3 B Ca-138 2, 3DCIPh BRA74 C Ca-139 H 5-Ind Aa-2 BRA75 C Ca-140 H H 1 Aa-5 BRA75 C Ca-141 H H 5-Bzt Aa-38 BRA75 C Ca-142 H H 1Me-5-Ind Aa-3 BRA76 0 Ca-143 2, 5DCIPh H H 1Me-5-lHldz Aa-5 BRA76 C Ca-144 2, 6DCIPh H H 1 Ca-145 3, 4DCIPh H H 2-Nap Aa-1 BRA78 C Ca-146 H H 5-Ind Aa-2 BRA78 C Ca-147 H H 1Me-5-Ind Aa-3 BRA78 Ca-148 3, 4DCIPh H H lMe~5~1Hldz Aa-5 BRA78 C Ca-149 H H 2-Nap Aa-1 BRA79 C Ca-150 H H 1Me-5-Ind. Aa-3 BRA79 lT Ca-151 BRA79 C Ca-152 2FPh H H 2-Nap Aa-1 BRA32 C Ca-153 2FPh H H 1 BRA32 0 Ca-154 2FPh H H 5-1 Aa-4 BRA32 _ Ca-155 2FPh H H 1 Ca-156 2FPh H H 5-Bzt Aa-38 BRA32 Ca-157 2FPh H H 3-Qu Aa-7 Ca-158 3FPh H H 5-Ind Aa-2 BRA33 Ca-159 3FPh H Aa-4 BRA33 Ca-160 3FPh H H 1 Aa-5 BRA33 C LumtiTable-Ca-4 Exp. Rx Y X -LMS method RTime Mass Ca-161 3FPh H H 3-Qu Ca-162 4FPh H H 2-Nap BRA34 C Ca-163 4FPh H H Aa-2 BRA34 C Ca-164 4FPh H Aa-4 BRA34 Ca-165 4FPh H H Aa-5 B Ca-166 4FPh H H 3-Qu Aa-7 BRA34 Ca-167 3DFPh H H 2-Nap Aa-1 BRA80 C 1) Ca-168 3DFPh H H 5-Ind _ Ca-169 3DFPh H H 1Me-5-lHIdz Aa-5 BRA80 Ca-170 2, 4DFPh H H 2-Nap Aa-1 BRA81 C Ca-171 4DFPh H H 5-Ind Aa-2 BRA81 C Ca-172 2, 4DFPh H H _1Me-5-lnd Ca-173 2, 4DFPh Aa-5 BRA81 Ca-174 2, 5DFPh H 2-Nap Aa-1 BRA82 C Ca-175 2, 5DFPh H H 1Me-5-Ind Aa-3 BRA82 C Ca-176 2, 5DFPh H H _lMe-5-lHldz Aa-5 BRA82 Ca-177 2, 6DFPh H H 2-Nap Aa-1 BRA83 C Ca-178 6DFPh H H 1Me-5-Irtd Aa-3 BRA83 C Ca-179 2, 6DFPh H H 5-1 Aa-4 BRA83 C Ca-180 2, 6DFPh H H 1Me-5-1Hldz Aa-5 BRA83 0 Ca-181 3, 4DFPh H H 2-Nap Aa-1 BRA84 C Ca-182 3, 4DFPh H H 5-Ind Aa-2 BRA84 C Ca-183 4DFPh H H 1Me-5-lHldz Aa-5 BRA84 C Ca-184 3, 5DFPh H H 2-Nap Aa-1 BRA85 C Ca-185 5DFPh H i-t Aa-3 BRASS Ca-186 5DFPh H H 5~1old Aa-4 BRA85 C Ca-187 5DFPh H H 1Me-5-lHIdz Aa-5 BRA85 0 Ca-188 2, 3 (CF3) 2Ph H H 2-Nap Aa-1 BRA63 Ca-189 H H 1Me-5-Ind Ca-190 2, 3 (CF3) 2Ph H H Aa-5 BRA63 C Ca-191 91 (CF3) 2Ph H H 2-Nap Aa-1 BRA64 C Ca-192 4 (CF3) 2Ph H H 1 Aa-5 BRA64 C493 Ca-193 5 (CF3) 2Ph H H 2-Nap Aa-1 BRA65 C Ca-194 Aa-2 BRA65 C Ca-195 2, 5 (CF3) 2Ph H H BRA65 C Ca-196 H H 3-Qu Aa-7 BRA65 C 490 (M Ca-197 4 (CF3) 2Ph H H 2-Nap Aa-1 BRA66 C 489 (M Ca-198 3, 4 (CF3) 2Ph H H l Aa-3 BRA66 C 492 (M Ca-199 3, 4 (CF3) 2Ph H H 5-1 HIdz Aa-4 BRA66 C 479 (M% Ca-200 3, 4 (CF3) 2Ph H H 1 Aa-5 BRA66 C 493 (M Ca-201 3, 5 (CF3) 2Ph H H 5-Ind Aa-2 BRA17 C Ca-202 3, 5 (CF3) H H 5-1Hldz Aa-4 BRA17 Ca-203 3, 5 (CF3) 2Ph H H lMe-5-lHldz Aa-5 BRA17 C 493 (M Ca-204 2-Furyl H H 2-Nap Aa-1 BRA35 C 343 343 Ca-205 2-Furyl H H 5-Ind Aa-2 BRA35 C Ca-206 2-Furyl H H 1 Aa-5 BRA35 C 347 (M'+l) Ca-207 2-Furyl H H 3-Qu Aa-7 BF Ca-208 3-Fury H H 1 Me-5-Ind Aa-3 BRA67 C Ca-209 3-Furyl H H. 5-1 Aa-4 B Ca-210 H 1 Aa-5 BRA67 C 347 (M Ca-211 2-Thienyl H H 2-Nap Aa-1 BRA36 C 359 (M Ca-212 2-Thienyl H H 1Me-5-Ind 362 (M Ca-213 2-Thienyl H H 1Me-5-1Hldz BRA36 C 363 (M Ca-214 2-Thienyl H 1 Ca-215 3-Thienyl AR SM1 SM2 Table-Ca-5 Exp. Rx Y AR SM1 method Ca-216 3-Thieny) Ca-217 H H 5-1 HIdz Aa-4 BRA68 C349 Ca-218 H H Me-5-1 Hide. Aa-5 BRA68 Ca-219 3-Thienyl H H 5-Bzt Aa-38 BRA68 0 Ca-220 3-Thienyl H H 3-Qu Aa-7 BRA68 0 Ca-221 3-Then H Aa-28 BRA68 C377 Ca-222 2-Py H H 5-Ind Aa-2 BRA69 C Ca-223 2-puy H H 1 Me-5-1 NIdz Aa-5 BRA69 C +1) Ca-224 2-puy H H 5-Bzt Aa-38 BRA69 C Ca-225 3-Py H H 2-Nap Aa-1 BRA70 C ) Ca-226 3-Py H H 5-Ind Aa-2 BRAVO Ca-227 3-Py H H 1Me-5-Ind Aa-3 BRA70 C ) Ca-228 H H 1Me-5-1HMz BRA70 C Ca-229 3-Py H H BRA70 C Ca-230 4-Py H H 2-Nap Aa-1 BRA26 Pua-231 4-Py H H 5-Ind Ca-232 4-Py H H 1 BRA26 C Ca-233 4-Py H H 5-1 Aa-4 BRA26 C 1) Ca-234 4-Py H H 1Me-5-lHIdz Aa-5 BRA26 C Ca-235 4-Py H H 5-Bzt Aa-38 BRA26 C361 Ca-236 4-Py H H 3-Qu BRA26 C355 Ca-237 4-Py H H 1 Aa-28 BRA26 C372 1' Ca-238 2DMAPh H H 2-Nap Aa-1 BRA86 C Ca-239 2DMAPh H H 5-Ind Aa-2 BRA86 Ca-240 2DMAPh H H 1 Aa-5 BRA86 C Ca-241 2DMAPh H H 5-Bzt Aa-38 BRA86 C Ca-242 2DMAPh H H 1 Aa-28 BRA86 C414 1' Ca-243 3DMAPh H H I Aa-3 BRA87 C Ca-244 3DMAPh H H 5-1 Aa-4 BRA87 0 Ca-245 3DMAPh H H 1 Me-5-1 HIdz Aa-5 BRA87 C400 +1 Ca-246 3DMAPh H H 5-Bzt Aa-38 BRA87 C Ca-247 3DMAPh H H 3-Qu Aa-7 BRA87 C397 -1) Ca-248 4DMAPh H H 2-Nap Aa-1 Ca-249 4DMAPh H H 1Me-5-tnd Aa-3 BRA21 C Ca-250 4DMAPh H H Me-5-1 HIdz Aa-5 BRA21 C Ca-251 4DMAPh H H 3-Qu Aa-7 BRA21 G Ca-252 4DMAPh H H I Aa-28 BRA21 c Ca-253 1-Nap H H 2-Nap Aa-1 Ca-254 1-Nap H H 5-Ind Aa-2 BRA16 Ca-255 1-Nap H H 1 Me-5-1 HIdz +1) Ca-256 1-Nap H H 5-Bzt Aa-38 BRA16 0 Ca-257 2-Nap H H 2-Nap Aa-'1 A1 Ca-258 2-Nap H H 1 Aa-3 BRA1 Ca-259 2-Nap H H 5-1 HIdz Aa-4 BRAL Ca-260 2-Nap H Me-5-1 HIdz Ca-261 2-Nap H H 5-Bzt Aa-38 BRA1 Ca-262 5-Ind H H 2-Nap Aa-1 BRA2 C Ca-263 5-wind H H 5-Ind Aa-2 BRA2 C381 l) Ca-264 5-Ind H H 1 Aa-5 BRA2 Ca-265 5-Ind H H 3-Qu Aa-7 BRA2 Ca-266 5-Ind H H'IEt-5-lHIdz Aa-28 BRA2 C Ca-267 LMe-5-1HHz H H 2-Nap Aa-1 BRA6 C +1) Ca-268 1 H H 1 Aa-3 BRA6 C410 Ca-269 1 Me-5-1 Hldz H H 1 Me-5-1 HIdz Aa-5 BRA6 Ca-270 1 Me-5-1 H H 5-Bzt Aa-38 BRA6 oY A O Tabie-Cb-1 _ Exp. Rx Y Zx AR SM1 SM2 LCMS _, Mass Cb-1 cPen H H 2-Nap Aa-1 BRA28 C345 Cb-2 cPen H H 5-Ind Aa-2 BRA28 c Cb-3 cPen H H 1 Me-5-Ind Aa-3 BRA28 C Cb-4 cPen H H 5-1 Aa-4 BRA28 C Cb-5 cPen H H 1 Aa-5 BRA28 C Cb-6 cPen H H 5-Bzt Aa-38 BRA28 C. Cb-7 cPen H H 3-Qu Aa-7 BRA28 C Cb-8 cPen H H 1 Aa-28 BRASS Cb-9 H 2-Nap Aa-1 BRA31 C Cb-10 H 5-Ind Aa-2 BRA31 C Cb-11 H H Aa-5 BRA31 C Cb-12 2-Nap Aa-1 BRA20 Cb-13 H 1 BRA20 C Cb-14 H 1 Aa-5 BRA20 +1 Cb-i H 5-Bzt Aa-38 BRA20 C340 Cob-16 H H Aa-28 BRA20 C Cb-17 H H 2-Nap Aa-1 BRA42 Cb-18 H H 5-Ind Aa-2 BRA42 C Cb-19 H H 1Me-5-tnd Aa-3 BRA42 C Cb-20 2-Indan H H 5-1 Aa-4 BRA42 C Cb-21 2-lndan H H 1 Aa-5 BRA42 C Cb-22 2-Indan H H 5-Bzt Aa-38 BRA42 0 Cb-23 2-Indan H H 3-Qu Aa-7 BRA42 G +1) Cb-24 2-Indan H H 1 Aa-28 BRA42 C411 Cb-25 4Me-2-Indan H H 5-Ind Aa-2 BRA43 Cb-26 4Me-2-Indan H H 5-1 Hldz Aa-4 BRA43 C Cb-27 4Me-2-Indan H H 1 BRA43 C Cb-28 4Me-2-Indan H H 3-Qu Aa-7 BRA43 C +1) Cb-29 5Me-2-Indan H 2-Nap Aa-1 BRA44 0 Cb-30 5Me-2-Indan H H 5-Ind Aa-2 BRA44 C Cb-31 5Me-2-Indan H H 5-1Hldz Aa-4 BRA44 C Cb-32 5Me-2-Indan H H 1 Aa-5 BRA44 C Cb-33 SMe-2-lndan H H 5-Bzt Aa-38 BRA44 C +1) Cb-34 5Me-2-Indan H H l Aa-28 BRA44 C Cb-35 4, 7DMe-2-Indan H H 5-Ind Aa-2 BRA45 C Cb-36 4, 7DMe-2-Indan H H 5-1 Aa-4 BRA45 C Cb-37 4, 7DMe-2-Indan H 1 Aa-5 BRA45 C Cb-38 5, 6DMe-2-Indan H H 2-Nap BRA46 C Cb-39 5, 6DMe-2-Indan H H 1Me-S-1Hldz Aa-5 BRA46 C Cb-40 5F-2-Indan H H 2-Nap Aa-1 BRA47 C Cb-41 5F-2-Indan H H 5-Ind Aa-2 _ Cb-42 5F-2-Indan H H 5-1 Hldz Aa-4 BRA47 C Cb-43 5F-2-Indan H H 1Me-S-1 Cb-44 5F-2-Indan H H 5-Bzt Aa-38 BRA47 C Cb-45 5F-2-Indan H H 3-Qu Aa-7 BRA47 C Cb-46 5F-2-Indan H H 1Et-S-1 Aa-28 BRA47 C Cb-47 4F-2-Indan H H 2-Nap Aa-1 BRA48 C Cb-48 4F-2-Indan H H 1 Me-5-Ind Aa-3 BRA48 C Cb-49 4F-2-Indan Aa-5 BRA48 C Cb-50 4, 7DF-2-Indan H H 2-Nap Aa-1 BRA49 C ZxTable-Cb-2 _-_ -CS Exp. method Cb-51 4 7DF-2-Indan H H 1Me-5-Ind Aa-3 BRA49 C Cb-52 4, 7DF-2-Indan H H 1Me-5-lHldz Aa-5 BRA49 C Cb-53 5, 6DF-2-Indan H H 2-Nap Aa-1 BRA50 G Cb-54 5, 6DF-2-Indan H H 5-Ind Aa-2 BRA50 C Cb-55 5, 6DF-2-Indan H H 1Me-5-Ind Aa-3 BRA50 C Cb-56 5, 6DF-2-lndan H H 5-1 Aa-4 BRA50 419 Cb-57 5, 6DF-2-Indan H H 1 Aa-5 BRA50 C Cb-58 5, 6DF-2-lndan H H 5-Bzt Aa-38 BRA50 Cb-59 5, 6DF-2-Indan H H 3-Qu Aa-7 BRA50 C Cb-60 5, 6DF-2-Indan Aa-28 BRA50 Cb-61 4CI-2-Indan H H 5-Ind Aa-2 BRA51 C Cb-62 4CI-2-lndan H H 1 Aa-5 BRA51 Cb-63 4CI-2-Indan H H 5-Bzt Aa-38 BRA51 C +1) Cb-64 5CI-2-Indan H H 2-Nap Aa-1 B Cb-65 5CI-2-Indan H H 5-Ind Aa-2 BRA52 C Cb-66 5C1-2-Indan H H 1 BRA52 C Cb-67 5CI-2-Indan H H 3-Qu Aa-7 BRA52 C 428 Cb-68 5CI-2-Indan H H 1 Aa-28 BRA52 C 445 Cb-69 4, 7DCI-2-Indan H H 2-Nap Aa-1 BRA53 c Cb-70 47DCI-2-lndan H H 5-Ind Aa-2 BRA53 C Cb-71 4, 7DCI-2-Indan H H Aa-5 BRA53 0-1466 Cb-72 5, 6DCI-2-Indan H H 2-Nap Aa-1 BRA54 C Cb-73 5, 6DCI-2-Indan H H 1Me-5-Ind Aa-3 BRA54 C Cb-74 5, 6DCI-2-lndan H H 1 Aa-5 BRA54 C Cb-75 5, 6DCì-2-lndan H H 5-Bzt Aa-38 BRA54 C Cb-76 5, 6DCI-2-Indan H H 3-Qu Aa-7 BRA54 C Cb-77 5, 6DCI-2-Indan H H 1Et-5-1 Aa-28 BRA54 Cb-78 4MeO-2-Indan H H 5-Ind Aa-2 BRA55 C Cb-79 4MeO-2-Indan H H 5-1 Aa-4 BRA55 C. Cb-80 4MeO-2-Indan H H 1 Aa-5 BRA55 C Cb-81 5MeO-2-Indan H H 2-Nap Aa-1 BRA56 Cb-82 5MeO-2-Indan H H 5-Ind Aa-2 BRA56 Cb-83 5MeO-2-Indan H H 1 Aa-5 BRA56 C Cb-84 5MeO-2-Indan H H 5-Bzt Aa-38 BRA56 C Cb-90 H H 2-Nap Aa-1 BRA57 C Cb-91 5, 6DMeO-2-Indan H H 1 BRA57 C Cb-92 5, 6DMeO-2-Indan H H 1 Aa-5 BRA57 457 Cb-93 5, 6DMeO-2-Indan H H 5-Bzt Aa-38 BRA57 C Cb-94 5, 6DMeO-2-Indan H H 3-Qu Aa-7 BRA57 Cb-95 5, 6-DMeO-2-Indan H 1 BRA57 C Cb-85 H H 2-Nap Aa-1 BRA58 C Cb-86 H H 5-Ind Aa-2 BRA58 C Cb-87 cHex H H 1 Aa-3 BRA58 C Cb-88 cHex H H 5-1Hldz Aa-4 BRA58 C +1) Cb-89 [Reference Examples: Intermediate Ab-1 to Ab-47] Synthesis of methyl 3- [4- (4, 4,5, 5-tetramethyl-1, 3,2-dioxaborolan-2-yl)-3- (naphthalen-2-yl)phenyl]propionate (Intermediate Ab-1) Compound No. Aa-1 (253.2 mg), bispinacolate diboron (202.6mg, Ald), PdCl2 (dppf) (43. 4 mg) and potassium acetate (289 mg) were added to DMF (5.7 ml), and stirred with heating at 80°C for 20 hours under argon gas atmosphere. The reaction mixture was added with ethyl acetate (200 ml), washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane : ethyl acetate 4: 1) to obtain the title compound (Intermediate Ab-1, 194.6 mg).
Typical examples of the compounds of the present invention including those mentioned above that can be obtained by reacting and treating corresponding starting compounds according to the synthesis method of Intermediate Ab-1 are shown in Table-Ab-1.
In the column indicated as"Mass"in the table, data of mass spectra measured by fast atom bombardment mass spectrometry (FAB-MS) are shown. - -Me o Table-Ab-1 Exp. AR Ab-1 2-Nap 417 (M 421 (M Ab-2 5-tnd'406 l) Ab-26 5-1 407 (M Ab-3 lMe-5-lnd Ab-27 1 421 (M Ab-4 5-1 407 (M Ab-28 1 435 (M Ab-5 1 421 (M Ab-29 1 449 (M+1) Ab-6 5-BF 410 (M Ab-30 2Me-5-2Hldz Ab-7 3-Qu 418 (M 407 (M Ab-8 1-Nap 417 (M Ab-32 1Me-6-lHIdz 421 (M Ab-9 6MeO-2-Nap Ab-33 3Me-5-lHldz 421 (M++1) Ab-10 6 (Me2N)-2-Nap Ab-34 1, 3DMe-5-1 435 (M Ab-11 406 (M++1'Ab-35 Ab-12 1 420 (M++1) 3DMe-5-BF 435 Ab-13 406 (M Ab-37 5-2ABzt 439 (M Ab-14 420 (M Ab-38 5-Bzt 434 (Mt+l) Ab-15 6 2Me-5-Bzt 438 (M++1) Ab-16 420 (M 2DMe-5-2ABzt 467 (M Ab-17 3-Ind 406 (M++1) 6-2ABzt 439 (M Ab-1881 420 (M*+'1) Ab-42 6-Bzt 434 (M++1) Ab-19 438 (M++1) Ab-20 lcPen-5-Ind 6-Qu 418 (M++l Ab-21 3Me-5-Ind 420 (M Ab-22 Ab-46 2-BF 407 (M++1) Ab-23 1, 123triMe-51nd Ab-24 T AR[Example Da-1] Synthesis of methyl 3- [4- (phenylmethyl)-3- (naphthalen-2-yl) phenyl] propionate (Compound No. Da-1) According to a procedure described in literature (S. Chowdhury et al., Tetrahedron. Lett. , 1999, p. 7599), (Ph3P) 4Pd (14.8 mg) and a solution of benzyl bromide (corresponding to the substance mentioned in the column of SM2 in Table- Da-1 mentioned later) in dimethoxyethane (1.3 ml) were stirred with heating at 50°C for 10 minutes under argon atmosphere, then added with Compound Ab-1 (52.4 mg, corresponding to the substance mentioned in the column of SM1 in Table- Da-1 mentioned later), and 2 N sodium carbonate (160 g 1), and refluxed by heating for 58 hours. The reaction mixture was added with ethyl acetate (60 ml), washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, dried, and then concentrated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 8: 1) to obtain the title compound (Compound No. Da-1, 33.2 mg).
[Example Da-2] Synthesis of 3- [4- (phenylmethyl) -3- (naphthalen-2-yl) phenyl] propionic acid (Compound No. Da-2) According to the procedure described in the synthesis method of Compound Ca-2 provided that the reaction was performed for 3 hours, Compound No. Da-1 (28.2 mg) and 2 N aqueous sodium hydroxide (38 g 1) were reacted and treated to obtain the title compound (Compound No. Da-2, 23.7 mg).
Examples Da-1 to Da-70] Typical examples of the compounds of the present invention including those mentioned in the examples described above, that can be obtained by reacting and treating corresponding starting compounds according to the methods described in Examples Da-1 and Da-2, are shown in Table-Da-1 and Table-Da-2.
The substances mentioned in the columns of"SMl"in the tables correspond to reaction intermediates, and those mentioned in the columns of"SM2"in the tables correspond to the acid halide mentioned in Example Da-1. The halide reagents mentioned in the columns of"SM2"with the symbols of"HAL (number))" are those mentioned in Table-Ha. The regents for which cells of the columns of "Manufacturer"are blank in the tables are synthesized according to a method described in ordinary chemical literature.
Table-Ha Reagent Name of reagent HAL-1 Benzyl HAL-2 4-Methoxybenzyl bromide HAL-3 3-Methoxybenzyl Ald bromide HAL-4 bromide HAL-5 bromide Aid HAL-6 3-Methylbenzyl bromide Ald HAL-7 2-Methylbenzyl bromide Aid HAL-8 4-Trifluoromethylbenzyl bromide HAL-9 bromide HAL-10 bromide HAL-11 bromide Aid HAL-12 bromide Aid HAL-13 HAL-14 HAL-15 bromide Aid HAL-15 bromide Aid HAL-16 bromide Ald HAL-17 ethane HAt18 phenyl) ethane HAL-19 phenyl) ethane HAL-20 1-Bromo-2-(2-chloro phenyl) ethane HAL-21 1-Bromo-2- aminophenyl) ethane HAL-22 Benzoyl HAL-23 Acetyl HAL-24 i-Butyryl HAL-25 Cyclohexylcarbonyl Aid chloride HAL-26 chloride HAL-27 chloride HAL-28 4-Chlorobenzoyl TCI chloride HAL-29 Phenylacetyl WAKO HAL-30 chloride 2 zx O Table-Da-1 Exp. Rx Y Zx/. R method Da-1 2-Nap Ab-1 HAL-1 D D Da-2 H 2-Nap Da-1-0 Da-3 H 5-Ind Ab-2 HAL-1 Da-4 Ph Da-5 Ph Me H 1 Me-5-Ind Ab-3 Ha-1 C Da-6 H 1 Da-7 H 5-lHldz Ab-4 Ha-1 Da-8 Ph H H 5-lHIdz Da-9 Ph. Me H 1 Da-10 H 1Me-5-1HHz D Da-11 4MeOPh H H 2-Nap Da-12 4MeOPh H H 5-Ind Ab-2 HAL-2 Da-13 H H 1 Ab-5 HAL-2 Da-14 3MeOPh H H 2-Nap HAL-3 C Da-15 H H 5-Ind Ab-2 HAL-3 Da-16 3MeOPh H H 1 HAL-3 Da-17 2MeOPh H H 2-Nap Ab-1 HAL-4 Da-18 2MeOPh H H 5-Ind Ab-2 HAL-4 Da-19 2MeOPh H H 1 Da-20 4MePh H H 2-Nap Ab-1 HAL-5 C Da-21 4MePh H H 5-Ind Ab-2 HAL-5 Da-22 4MePh H H 1 Da-23 3MePh H H Da-24 3MePh H H 5-Ind Ab-2 HAL-6 Da-25 3MePh H H 1 Ab-5 HAL-6 Da-26 2MePh H H 2-Nap Ab-1 HAI-7 0 Da-27 2MePh H H 5-Ind Ab-2 HAI-7 Da-28 2MePh Ab-5 HAI-7 Da-29 4DFPh H H 2-Nap Da-30 4CF3Ph H H 5-Ind Ab-2 HAL-8 Da-31 4CF3Ph H H 1 Da-32 3CF3Ph H H 2-Nap Ab-1 HAL-9 Da-33 3CF3Ph H H 5-Ind Ab-2 HAL-9 Da-34 3CF3Ph H H 1 Ab-5 HAL-9 Da-35 2CF3Ph Da-36 2CF3Ph H H 5-Ind Ab-2 HAL-10 Da-37 2CF3Ph H H 1 Ab-5 HAL-10 Da-38 4CIPh H H 2-Nap Ab-1 HAL-11 +1) Da-39 4CIPh H H 5-Ind Ab-2 HAL-11 C390 Da-40 4CIPh H H 1 Ab-5 HAL-11 Da-41 3CIPh 2-Nap Ab-1 HAL-12 Da-42 3CIPh H H 5-Ind Ab-2 HAL-12 Da-43 3CIPh H H 1 Ab-5 HAL-12 Da-44 2CIPh H H 2-Nap Da-45 2CIPh H Ab-2 HAL-13 Da-46 2CIPh H 1 Me-5-1 Ab-5 HAL-13 Da-47 4FPh H H 2-Nap Da-48 4FPh H H 5-Ind Ab-2 HAL-14 Da-49 4FPh H H 1 Ab-5 HAtl Da-50 3FPh H H 2-Nap Ab-1 ManufacturerTable-Da-2 Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Da-51 3FPh H H 5-Ind Ab-2 HAL-15 Da-52 3FPh H H 1 Ab-5 HAL-15 Da-53 2FPh H H 2-Nap Ab-1 HAL-16 Da-54 H H 5-Ind Ab-2 HAL-16 Da-55 2FPh H H 1 Ab-5 HAL-16 Da-56 Bn H 2-Nap Ab-1 HAL-17 Da-57 Bn H H 5-Ind Ab-2 Da-58 Da-59 4CIBn H H 2-Nap Ab-1 HAL-18 Da-60 4CIBn H H 5-Ind Ab-2 HAL-18 Da-61 4CIBn H H 1 Ab-5 HAL-18 7 Da-62 3CIBn H H 2-Nap Ab-1 HAL-19 C Da-63 3CIBn H H 5-Ind Ab-2 HAL-19 Da-64 3CIBn H 1 Me-5-1 Da-65 2CIBn H H 2-Nap Ab-1 HAL-20 Da-66 2CIBn H H 5-Ind Ab-2 HAL-20 Da-67 2CIBn H 1 Me-5-1 Da-68 4DMABn H H 2-Nap Ab-1 HAL-21 Da-69 4DMABn H H 5-tond Ab-2 HAL-21 _ Da-70 4DMABn H Ab-5 HAL-21 [Example Ea-1] Synthesis of methyl 3- [4- (phenylcarbonyl)-3- (naphthalen-2-yl) phenyl] propionate (Compound No. Ea-1) According to a procedure described in literature (Y. Urawa et al, Tetrahedron. Lett. , 2003, p. 271), Compound Ab-1 (112. 1mg, corresponding to the substance mentioned in the column of SM1 in Table-Ea-1 mentioned later), dichlorobis (triphenylphosphine) palladium (18.9 mg, KANTO), and a solution of potassium phosphate (147.1 mg) in toluene (2.6 ml) were added with benzoyl chloride (47 u g, corresponding to the substance mentioned in the column of SM2 in Table-Ea-1), and stirred with heating at 110°C for 48 hours under nitrogen atmosphere. The reaction mixture was washed successively with saturated aqueous sodium hydrogencarbonate, water and saturated brine, dried, and then concentrated under reduced pressure. The residue was purified by flash column chromatography (hexane: ethyl acetate = 7: 1) to obtain the title compound (Compound No. Ea-1, 88. 3 mg).
[Example Ea-2] Synthesis of 3- [4-phenylcarbonyl-3- (naphthalen-2-yl) phenyl] propionic acid (Compound No. Ea-2) According to the procedure described in the synthesis method of Compound Ca-2 with the modification that the reaction was carried out for 3 hour, Compound No. Ea-1 (82.6 mg) and 2 N aqueous sodium hydroxide (105 ml) were reacted and treated to obtain the title compound (Compound No. Ea-2,70. 7 mg).
[Examples Ea-1 to Ea-34] Typical examples of the compounds of the present invention including those mentioned in the examples described above, that can be obtained by reacting and treating corresponding starting compounds according to the methods described in Examples Ea-1 and Ea-2, are shown in Table-Ea-1.
The substances mentioned in the column of"SM1"in the table correspond to reaction intermediates, and those mentioned in the column of"SM2"in the table correspond to acid chlorides mentioned in Table Ea-1. The acid chlorides mentioned with the symbols of"HAL (number) "in the column of"SM2"are those mentioned in Table-Ha. Zx Rx O \ I O Table-Ea-1 . Exp. Rx Y Zx AR SM1 SM2 method Mass Ea-1 H 2-Nap Ab-1 HAL-22 C Ea-2 H 2-Nap Ea-1-0381 Ea-3 H 5-Ind Ab-2 HAL-22 Ea-4 Ea-4 Ea-5 Ph Ab-3 HAL-22 _ Ea-6 H 1 Ea-7 H 5-1 Ab-4 HAL-22 Ea-8 H 5-1 Ea-9 H IMe-5-lHldz Ea-10 H H _ Ea-11 H 2-Nap Ab-1 HAt23 Ea-12 Ab-2 HAL-23 308 Ea-13 H H Ab-5 HAL-23 Ea-14 H 2-Nap Ab-1 HAL-24 C Ea-15 iBu H H 5-Ind Ab-2 HAL-24 Ea-16 H 1Me-5-1HIdz Ab-5 HAL-24 365 Ea-17 H H 2-Nap Ab-1 HAL-25 C Ea-18 H 5-Ind Ab-2 HAL-25 Ea-19 H H 1 Ab-5 HAL-25 Ea-20 4MeOPh H Ea-21 4MeOPh H H 5-lnd Ab-2 HAL-26 C Ea-22 4MeOPh H H 1 Ab-5 HAL-26 Ea-23 4MePh H H 2-Nap Ab-1 HAL-27 Ea-24 4MePh H H 5-Ind Ea-25 4MePh H H 1 Ab-5 HAL-27 Ea-26 4CIPh H H 2-Nap Ab-1 HAL-28 Ea-27 4CIPh H 5-Ind Ab-2 Ea-28 4C H 1 Me-5-1 Ab-5 HAL-28 Ea-29 H H 2-Nap Ab-1 HAL-29 Ea-30 H 5-Ind Ab-2 HAL-29 Ea-31 Bn H H Ab-5 HAL-29 Ea-32 1 H H 2-Nap Ab-1 HAL-30 C Ea-33 1PhEt H H 5-Ind Ab-2 HAL-30 C Ea-34 [Reference Examples : Intermediate Ac-1 and Ac-2] Synthesis of t-butyldimethylsilyl 3- [3-bromo-4- (t- butyldimethylsilyloxy) phenyllacrylate (Intermediate Ac-1) According to the procedure described in the synthesis method of Intermediate 43, 3- [3-bromo-4-hydroxylphenyll acrylic acid (12. 01 g) obtainable from 4-hydroxybenzaldehyde (TCI) by a method known from literature (Y. Nagao et al. , Tetrahedron Lett. , 1980, p. 4931) was reacted with imidazole (16.01 g) and t- butyldimethylsilyl chloride (7.43 g) and treated to obtain the title compound (Intermediate Ac-1,17. 43 g).
Synthesis of 3- [3-bromo-4- (t-butyldimethylsilyloxy) phenyl acrylic acid (Intermediate Ac-2) A solution of Compound Ac-1 (17.43 g) in methanol (100 ml) was added with 1 N hydrochloric acid (5 ml), and stirred at room temperature for 3 hours. The reaction solution was extracted with ethyl acetate (500 ml), and washed with saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane: ethyl acetate = 6 : 1) to obtain the title compound (Compound No. Ac-2,14. 60 g).
Example Ga-l] Synthesis of methyl 3- [3- (lH-indol-5-yl)-4- (3-pyridinemethyloxy) phenyl] acrylate (Compound No. Ga-1) (Step 1) A solution of Compound Ac-2 (3. 06 g), diisopropyl carbodiimide (henceforth abbreviated as"DIC", 1.33 ml) and dimethylaminopyridine (86. 8 mg) in DMF (100 ml) was added with SynPhase-PS-D-series Lantern, Hydroxymethylphenoxy Linker (henceforth abbreviated as"PSL", 0.035 mmol per lantern, 81 lanterns, Mimotopes), and left standing at room temperature for 16 hours. After the reaction mixture was removed, PSL was washed successively with DMF (100 ml), methanol (100 ml), dichloromethane (100 ml), and THF (100 ml) three times for each, and dried under reduced pressure.
PSL (81 lanterns mentioned above) was added to a solution of tetrabutylammonium fluoride (8. 5 ml, Ald, 1 N THF solution) in THF (80 ml), and left standing at room temperature for 23 hours. After the reaction mixture was removed, PSL was successively washed with DMF (100 ml) three times, alternately with DMF : water : acetic acid (75 : 25 : 1,100 ml) and methanol: water: acetic acid (75: 25: 1,100 ml) twice for each, alternately with DMF: water (4: 1,100 ml) and methanol : water (4: 1,100 ml) twice for each, and with THF (100 ml), chloroform (100 ml), DMF (100 ml), and chloroform (100 ml) twice for each, and then dried under reduced pressure to obtain PLS-1 (81 lanterns).
(Step 2) PSL-1 (3 lanterns out of those mentioned above) was added to a mixed solution of 3-pyridinemethanol (147. 6 u 1, corresponding to the substance mentioned in the column of SM1 in Table-Ga-1 mentioned later), DBAB (242. 1mg, Sigma) and PhsP (275.6 mg, KANTO) in dehydrated THF (3.24 ml), and left standing at room temperature for 15 hours. After the reaction mixture was removed, PSL was successively washed with THF (3.5 ml) and DMF (3. 5 ml) four times for each, alternately with methanol (3.5 ml) and DMF (3.5 ml) twice for each, alternately with DMF (3.5 ml) and dichloromethane (3.5 ml) twice for each, with dichloromethane (3.5 ml) twice, and dried under reduced pressure to obtain PSL-2 (3 vials).
(Step 3) PSL-2 (1 lantern out of those mentioned above) was added to a mixed solution of 1H-indole-5-boronic acid (11.3 mg, corresponding to the substance mentioned in the column of SM2 in Table-Ga-1 mentioned later), (Ph3P) 4Pd (8.1 mg), and 2 N aqueous cesium carbonate (176, u 1) in DMF (800, u 1), and heated at 80'C for 18 hours under argon atmosphere. After the reaction mixture was removed, PSL was successively washed with DMF (1.0 ml) four times, with methanol (1.0 ml) twice, alternately with DMF (1.0 ml) and methanol (1.0 ml) twice for each, alternately with DMF (1.0 ml) and dichloromethane (1.0 ml) twice for each, and with dichloromethane (1.0 ml) twice, and dried under reduced pressure. This PSL was added to a solution of sodium methoxide (175, u 1, WAKO, 1 N solution in methanol) in THF : methanol (2: 1,1. 5 ml), and left standing at room temperature for 19 hours. After the reaction, PSL was removed, and the reaction solution was added with water (500, u 1), and stirred with heating at 60°C for 3 hours. The reaction solution was concentrated under reduced pressure, then added with water (200 rye 1) and chloroform (1 ml), and passed through a diatomaceous earth column, and the obtained filtrate was concentrated under reduced pressure to obtain the title compound (Compound No. Ga-1, 10.6 mg).
[Examples Ga-1 to Ga-55] Typical examples of the compounds of the present invention including those mentioned in the examples described above, that can be obtained by reacting and treating corresponding starting compounds according to the method described in Example Ga-1, are shown in Table-Ga-1 and Table-Ga-2.
The substances mentioned in the columns of"SMl"in the tables correspond to the alcohol reagent mentioned in Example Ga-1, and those mentioned in the columns of"SM2"in the tables correspond to the boronic acid reagent mentioned in Table Ga-1. The alcohol reagents mentioned in the columns of"SM1"with the symbols of"ALC (number) )"are those mentioned in Table'1. The boronic acid reagents mentioned with the symbols of"BRA (number) )"in the columns of"SM2" are those mentioned in Table-Ba-1 and Table-Ba-2.
Table-I Reagent Name of reagent Manufacture Name of reagent ALC-1 Cyclopentanol KANTO ALC-16 TCI ALC-2 Cyclohexanol Ald 4-methylthiazol ALC-3 Benzyl ALC-4 2-Methyl-1-propyl acetate TCI ALC-5 4-Fluorophenetyl alcohol ALC-6 1-Phenylethanol Dimethylaminoethoxy) ALC-7 TCI ALC-8 2-Hydroxy indane ALC-9 2-Hydroxymethyl-TCI ALC-24 2-Chlorobenzyl aicohol 1, 4-benzodioxane ALC-10 ethanol ALC-11 3-Pyridine methanol TCI ALC-26 4-Chlorobenzyl ALC-12 ALC-27 2-Methoxybenzyl TCI alcohol ALC-13 alcohol ALC-14 ALC-29 4-Methoxybenzyl TCI alcohol ALC-15 Rx ou Au Table-Ga-1 Exp. RxO Y Zx AR SM1 SM2 method RTime Mass Ga-1 3PyMeO H H 5-Ind BRA2 A 3. 27 37 Ga-2 2 (PhS) EtO H H 5-Ind ALC-16 BRA2 Ga-3 NS° H H 5-Ind ALC-17 BRA2 A 3. 07 405 (M++1) Ga-4 nBuO H H 5-Ind Ga-5 oNO H 5-Ind ALC-21 BRA2 Ga-6 Ga-7 cHexO H H 5-Ind ALC-2 BRA2 Ga-8 PhMeO H H 5-Ind ALC-3 BRA2 A 3. 79 356 (M++1 Ga-9 cPenO H H 2-BF ALC-1 BRA18 Ga-10 cHexO H H 2-BF ALC-2 BRA18 Ga-11 H H 2-BF ALC-8 BRA18 A 3. 85 397 +1) Ga-12 H H 2-BF ALC-11 BRA18 Ga-13 2 (PhS) H H 2-BF ALC-16 BRA18 A 3. 61 417 (M++l) Ga-14 N H H 2-BF ALC-17 BRA18 -s Ga-15 nBuO H I Ga-16 o H 2-BF ALC-21 BRA18 Ga-17 cPenO H H 1 Ga-18 H H 1 3. 74 377 (M++l) Ga-19 H H 1 BRA6 Ga-20 3PyMeO H H 1Me-5-1 Ga-21 2 (PhS) EtO H H 1 BRA6 Ga-22 t5 H H 1 BRA6 vs Ga-23 Ga-24 H 1 Me-5-1 Hldz BRA6 Ga-25 1-Nap ALC-11 Ga-26 2 (PhS) EtO H H 1-Nap Ga-27 < H H 1-Nap ALC-17 -S Ga-28 nBuO H H 1-Nap ALC-18 BRA16 Ga-29 N0 H H 1-Nap ALC-21 BRA16 Ga-30'IPhEtO H H ReagentTable-Ga-2 Exp. RxO Y Zx AR SM1 SM2 LCMS method RTime Mass Ga-31 1 H 2-BF ALC-6 BRA18 Ga-32 1 H H 1 ALC-6 BRA6 A 3. 55 Ga-33 1 H H 1-Nap ALC-6 BRA16 Ga-34 1 H 2-Nap ALC-6 BRA1 Ga-35 1 H H 2-Nap ALC-6 BRA1 C Ga-36 lPhEtO H 5-Ind ALC-6 8RA2 Ga-37 2CIPhMeO H H 2-Nap ALC-24 BRA1 Ga-38 2CIPhMeO H H 5-Ind ALC-24 BRA2 Ga-39 3CIPhMeO H H 2-Nap ALC-25 BRA1 C Ga-40 3CIPhMeO H H 5-Ind ALC-25 BRA2 Ga-41 4CIPhMeO H H 2-Nap ALC-26 BRA1 Ga-42 4CIPhMeO H H 5-Ind ALC-26 Ga-43 2MeOPhMeO H H 2-Nap ALC-27 BRA1 Ga-44 2MeOPhMeO H H 5-Ind ALC-27 BRA2 Ga-45 3MeOPhMeO H H 2-Nap ALC-28 BRA1 Ga-46 3MeOPhMeO H H 5-land ALC-28 BRA2 Ga-47 4MeOPhMeO H H 2-Nap ALC-29 BRA1 Ga-48 4MeOPhMeO H H 5-Ind BRA2 Ga-49 nBuO H H 3-Qu ALC-18 BRA10 C Ga-50 nBuO H H 3-Thienyl AL. Ga-51 nBuO H H 4-Py ALC-18 BRA26 Ga-52 nBuO H H oPen ALC-18 BRA28 Ga-53 nBuO H H Ga-54 nBuO H H 3FPh ALC-18 BRA33 Ga-55 [Reference Examples : Intermediate s-1 to s-52] Synthesis of methyl 3- [4- (4-methylphenylthio)-3-nitrophenyl] acrylate (Intermediate s-1) (Synthesis method SF) A solution of 3- [4- (4-methylphenylthio)-3-nitrophenyl] acrylic acid (631 mg, MAYB) in a mixture of methanol (12.6 ml), ethyl acetate (6.3 ml) and THF (6.3 ml) was added dropwise to methanol (12.6 ml) beforehand under ice cooling, and then the mixture was added with a solution of thionyl chloride (735 u 1, KANTO) in methanol (50 ml) under ice cooling, stirred for 30 minutes, then warmed to room temperature, and further stirred for 15.5 hours. The reaction mixture was poured into aqueous sodium hydrogencarbonate (50 ml) for neutralization, and extracted with ethyl acetate (50 ml), and the organic layer was washed with saturated brine.
The organic layer was dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate s-1, 659 mg).
Synthesis of methyl 3- [4- (4-methylphenylthio)-3-nitrophenyllpropionate (Intermediate s-2) (Synthesis method SD1) A solution of Intermediate s-1 (494 mg) in ethyl acetate (75 ml) was added with 10% palladium hydroxide/carbon (150 mg, NE CHEMCAT), and stirred at room temperature for 14 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure.
The residue was dissolved in methanol (75 ml) again, added with 5 N hydrochloric acid (600, u 1) and 10% palladium hydroxide/carbon (151 mg), and stirred at room temperature for 22 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Intermediate s-2, 419 mg).
Synthesis of methyl 3- [3-bromo-4- (4-methylphenylthio) phenyl] propionate (Intermediate s-3) (Synthesis method SEl) A solution of hydrobromic acid (690, u 1) in methanol (3.2 ml) was added with a solution of Intermediate s-2 (362 mg) in methanol (3.2 ml) under ice cooling.
This mixture was added dropwise with an aqueous solution (320, u 1) of sodium nitrite (84 mg, WAKO).
An aqueous solution (3.2 ml) of copper (II) bromide (270 mg, WAKO) was heated to 40°C, added dropwise with the previously obtained solution over 20 minutes, and stirred at the same temperature for 1.5 hours.
The reaction mixture was extracted with ethyl acetate (40 ml). The organic layer was washed successively with water and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 9 : 1) to obtain the title compound (Intermediate s-3, 167 mg).
Synthesis of methyl 3-(3-bromo-4-fluorophenyl) acrylate (Intermediate s-4) (Synthesis method SF) According to the procedure described in the synthesis method of Intermediate n-1 (Synthesis method SF) provided that the reaction was performed for 1 hour, 3-bromo-4-fluorocinnamic acid (3.30 g, LANC) and thionyl chloride (1.5 ml, WAKO) were reacted and treated to obtain the title compound (Intermediate n- 25,3. 47 g).
Synthesis of methyl 3- [3-bromo-4- (4-methoxyphenylthio) phenyl] acrylate (Intermediate s-5) (Synthesis method SC) A solution of Intermediate s-4 (259.1 mg) in DMSO (4 ml) was added with potassium carbonate (156.9 mg) and p-methoxythiophenol (148 u 1, TCI), and stirred at 70°C for 16 hours. The reaction mixture was extracted with ethyl acetate (30 ml), and then the organic layer was washed successively with water and saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 8 : 1) to obtain the title compound (Intermediate s-5, 283.3 mg).
Synthesis of methyl 3- [3-bromo-4- (4-methoxyphenylthio) phenyl) propionate (Intermediate s-6) (Synthesis method SD2) According to a procedure described in literature [D. J. Hart et al., Journal of Organic Chemistry (J. Org. Chem. ), 1987, vol. 52, p. 4665], a solution of Intermediate s-5 (579.1 mg) in dimethoxyethane (40 ml) was added with p- toluenesulfonhydrazide (1.99 g, TCI), and refluxed by heating at 110°C. Then, the reaction mixture was added dropwise with an aqueous solution (40 ml) of sodium acetate (1.54 g, WAKO) over 1 hour, and further stirred for 3 hours. The reaction mixture was extracted with dichloromethane (150 ml), and the organic layer was washed with water, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 7 : 1) to obtain the title compound (Intermediate s-6, 583. 5 mg).
Synthesis of 3-bromo-4- (cyclopentylthio) benzaldehyde (Intermediate s-23) (Synthesis method SC) A solution of 3-bromo-4-fluorobenzaldehyde (517.4 mg) in DMSO (8 ml) was added with potassium carbonate (514.9 mg) and cyclopentanethiol (250, u 1, TCI), and stirred at 90°C for 17 hours. The reaction mixture was extracted with ethyl acetate (50 ml), and the organic layer was washed successively with water and saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 8 : 1) to obtain the title compound (Intermediate S-23, 644.7 mg).
Synthesis of ethyl 3- [3-bromo-4- (cyclopentylthio) phenyllacrylate (Intermediate s- 24) (Synthesis method SE2) A solution of Intermediate s-23 (243.7 mg) in 1,2-dimethoxyethane (8 ml) was added with ethyl diethylphosphonoacetate (300, 1, TCI), and added with 60% sodium hydride (49.8 mg) under ice cooling. The reaction mixture was stirred for 10 minutes, then warmed to room temperature, and stirred for 1 hour. The reaction mixture was added with water (5 ml) for quenching, added with dichloromethane (30 ml) for extraction, and washed with saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 4: 1) to obtain the title compound (Intermediate s-24, 286.2 mg).
Typical examples of the intermediates including those mentioned above that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table- Int. S-1 and Table-Int. S-2. In the tables, intermediate numbers are mentioned in the columns indicated as"Exp". In the tables, used methods among those described above are mentioned in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of"SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Further, the compounds indicated as "Single"in the columns of"Single or Double"in Table-Int. S-1 are compounds in which two of the carbon atoms binding the benzene ring and carbonyl group in the compounds are bound with a single bond, and those indicated as"Double"in the same are compounds in which two of the carbon atoms binding the benzene ring and carbonyl group in the compounds are bound with a double bond. Rx-S Table-Int. E-<-r. m c'no n Singte or LCMS Exp. SM2 Rx-S Double method RTime Mass Ints-5 4MeOPhS Me Double D 5. 87 378 +1) Int. s-6 SD2 Int. s-5 Me Single C Ints-7 s-4 2MeOPhSH 2MeOPhS Me Double Ints-8 Me Single C Int. s-9 SC Int. s-4 3MeOPhSH 3MeOPhS Me Double c Int. SD2 Ints-9 Me Single C 380 (M++1) Int. SC Int. s-4 2MePhSH 2MePhS Me Double Int. SD2 Jnt. s-1 Me Single D 5. 70 N. D Int. SC Int. s-4 3MePhSH 3MePhS Me Double C Int. SD2 Ints-l Me Single Int. s-15 SC Int. s-4 4MePhSH 4MePhS Me Double C Int. SD2 Ints-15 Int. Me Double C Int. s-18 SD2 Int. s-l Me Single C Int. SC Int. s-4 3FPhSH 3FPhS Me Double C Int. s-20 SD2 Int. Me Single C Int. s-21 SC Int. s-4 4FPhSH Me Double Ints-22 SD2 nt. Me Single C 370 (M++1) Int. s-24 SE2 Int. s-23 Me Double D 6. 35 340 (M+1) Int. s-25 SD2 Int. s-24 Me Single C Int. s-27 SE2 Int. s-26 Et Double Int. s-28 SD2 Int. s-27 Et Single C Ints-30 SE2 Ints-29 Et Double C Int. s-31 SD2 Int. s-30 Et Single C Int. s-33 SE2 Ints-32 iPrS Et Double C Int. s-34 SD2 Int. s-33 Et Single Ints-36 SE2 Int. Et Double Int. s-37 SD2 Int. Et Single C Int. s-39 SE2 Int. s-38 Me Double D 5. 86 330 (M++1) Int. s-40 SD2 Ints-39 _ Me Single D 6. 23 330 (M++1) Int. s-42 SE2 Ints-41 Me Double D 6. 18 376 (M+) Int. s-43 SD2 Int. s-42 Me Single D 6. 21 378 (M+) Int. s-45 SE2 Int. Et Double C 393 (M++1 Int. s-46 SD2 Int. s-45 Et Single C Int. s-48 SE2 Ints-47 4FBnS Et Int. s-49 SD2 Ints-48 4FBnS Et Single C Int. s-51 SE2 Int. Et Double C Int. s-52 SD2 Int. Et Single C Rx-S- _ Table-Int. Exp. Syn. SM1 SM2 Rx-S LCMS method Mass Int. s-23 SC Ints-26 Int. Ints-32 SC Int. s-35 SG Ints-38 SC Int. s-41 SC 2PhEtS C Ints-44 SC. 4MeOBnS C Int. s-47 SC Int. 2MeBnS 0 [Example S-a-1] Synthesis of methyl 3-13- (naphthalen-2-yl)-4- (4- methylphenylthio) phenyl] propionate (Compound No. N-a-l) (Synthesis method SB) A solution of Intermediate s-3 (146 mg) in toluene (2 ml) was added with 2- naphthaleneboronic acid (132.3 mg, TCI), 2 M aqueous sodium carbonate (600 u ml), methanol (500 g 1), and tetrakistriphenylphosphine palladium (0) (henceforth abbreviated as" (PhsP) 4Pd", 38 mg, Nacalai Tesque), and stirred at 80°C for 14.5 hours. The reaction mixture was added with ethyl acetate (40 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 4: 1) to obtain the title compound (Compound No. S-a-1, 78 mg).
Example S-a-2] Synthesis of 3- [3- (naphthalen-2-yl)-4- (4-methylphenylthio) phenyl] propionic acid (Compound No. S-a-2) (Synthesis method SA) A solution of the compound of Example S-a-1 (51 mg) in methanol (5.0 ml) was added with 2 N aqueous sodium hydroxide (130 u 1), and stirred at 60°C for 2 hours. The reaction mixture was concentrated under reduced pressure, then made acidic with 5% aqueous hydrochloric acid under ice cooling, and then extracted with ethyl acetate (30 ml). The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Compound No. S-a-2,47 mg).
[Example S-c-1] Synthesis of methyl 3- [4- (4-methoxyphenylthio)-3- (naphthalen-2- yl) phenyl] propionate (Compound No. S-c-1) (Synthesis method SD2) According to the procedure described in the synthesis method of Intermediate s-6 (Synthesis method), the compound of Example S-b-1 (3.01 g), p- toluenesulfonhydrazide (430.1 mg), and sodium acetate (380.4 mg) were reacted and treated to obtain the title compound (Compound-No. S-c-1, 95.1 mg).
[Examples S-a-1 to S-a-24, S-b-1 to S-b-138 and S-c-1 to S-c-138] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-S-A-1, Table-S-B-1 to Table-S-B-3 and Table-S-C-1 to Table-S-C-3. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of"SM1", and the starting compounds 2 are mentioned in the columns of"SM2". The boronic acid reagents shown with the symbols of"BRA (number) "in the columns of"SM2"are those mentioned in Table- Ba-1 and Table-Ba-2. Rx-, Table-S-A-1 _.". . Exp. Syn SM1 SM2 Rx Y AR method Mass S-a-1 SB Int. s-3 BRA1 4MePh Me 2-Nap G S-a-2 H 2-Nap S-a-3 SB Int. BRA2 4MePh Me 5-Ind C S-a-4 SA S-a-3 H 5-Ind C S-a-5 SB Int. s-3 BRA3 4MePh S-a-6 SA S-a-5 H 1 S-a-7, SB Int. s-3 BRA4 4MePh Me 1 S-a-8 SA S-a-7 H 1 Et-5-Ind S-a-9 SB Int. s-3 BRA5 4MePh Me 5-1 Hldz C S-a-10 SA S-a-9 H 5-1 Hldz C S-a-11 SB Int. s-3 BRA6 4MePh Me 1 S-a-12 SA S-a-11 H 1 S-a-13 SB Int. s-3 BRA7 4MePh S-a-14 SA S-a-13 H 1 S-a-15 SB Int. s-3 BRA8 4MePh Me 2Me-5-2HIdz C S-a-16 SA S-a-~ H 2Me-5-2HIdz S-a-17 SB Int. BRA9 4MePh Me 5-Bzt C S-a-18 SA S-a-17 H 5-Bzt C S-a-19 Int. s-3 BRA10 4MePh Me 3-Qu C S-a-20 SA S-a-19 H 3-Qu S-a-21 SB Int. 4MePh Me 6-Qu C S-a-22 SA S-a-21 4MePh H 6-Qu C S-a-23 SB Int. s-3 BRA12 4MePh Me 6-IQ S-a-24 SA N-a-23 H 6-IQ Rx-s--Y Table-S-B-1 Exp. Syn SM1 SM2 Rx Y method Mass S-b-1 SB Int. s-5 BRA1 4MeOPh Me 2-Nap S-b-2 SA S-b-I H 2-Nap C S-b-3 SB Int. s-5 BRA2 4MeOPh Me 5-Ind C S-b-4 SA H 5-lnd S-b-5 SB Int. s-5 BRA3 4MeOPh Me 1 S-b-6 SA S-b-5 H 1 S-b-7 SB Int. s-5 BRA4 4MeOPh Me 1 S-b-8 SA S-b-7 H 1 S-b-9 SB Int. s-5 BRA5 4MeOPh Me 5-1 HIdz S-b-10 SA S-b-9 H 5-1 Hldz C S-b-11 SB Int. s-5 BRA6 4MeOPh Me 1 S-b-12 SA S-b-11 H 7 S-b-13 SB Int. s-5 BRA7 4MeOPh Me 1 S-b-14 SA S-b-13 S-b-15 SB Int. s-5 BRA8 4MeOPh Me 2Me-5-2Hldz S-b-16 SA S-b-15 H 2Me-5-2HIdz S-b-17 SB lnt. 4MeOPh Me 5-Bzt C S-b-18 SA S-b-17 5-Bzt C S-b-19 Int. s-5 BRA10 4MeOPh Me 3-Qu C S-b-20 SA S-b-19 H 3-Qu C S-b-21 SB Ints-5 BRA11 4MeOPh Me 6-Qu C S-b-22 SA S-b-21 H 6-Qu C S-b-23 SB Int. s-5 BRA12 4MeOPh Me 6-IQ C S-b-24 SA S-b-23 H 6-IQ C414 S-b-25 SB Int. s-7 BRA1 2MeOPh Me 2-Nap C S-b-26 SA S-b-25 H 2-Nap C S-b-27 SB Int. BRA2 2MeOPh Me 5-Ind C S-b-28 SA S-b-27 H 5-Ind C S-b-29 SB Int. s-7 BRA5 2MeOPh Me e S-b-30 SA S-b-29 H 5-1 Hldz C S-b-31 SB Int. s-7 BRA10 Me 3-Qu C S-b-32 SA S-b-31 H 3-Qu C S-b-33 SB Int. s-9 BRA1 3MeOPh Me 2-Nap C S-b-34 SA S-b-33 H 2-Nap C S-b-35 SB Int. s-9 BRA3 S-b-36 SA S-b-35 H 1 S-b-37 SB Int. s-9 BRA6 Me 1 S-b-38 SA S-b-37 H 1 S-b-39 SB Int. s-9 BRA11 Me 6-Qu C S-b-40 SA S-b-39 H 6-Qu C S-b-41 SB Int. BRA2 2MePh Me 5-Ind S-b-42 SA S-b-41 H 5-Ind C S-b-43 SB 2MePh Me 1Me-5-Ind S-b-44 SA S-b-43 44- S-b-45 BRA5 2MePh Me 5-lHldz S S-b-46 SA S-b-45 s 0-YTable-S-B-2 LCMS Exp. Syn SM1 SM2 method RTime Mass S-b-47 SB Int. S-b-48 SA N-b-47 H 1 S-b-49 SB Int. s-13 3MePh Me 1 S-b-50 SA N-b-49 S-b-51 SB Int. s-13 BRA9 3MePh Me 5-Bzt C S-b-52 SA N-b-51 H 5-Bzt C S-b-53 SB Int. s-15 Me 2-Nap C S-b-54 SA N-b-53 S-b-55 SB Int. BRA2 4MePh Me 5-Ind C S-b-56 SA N-b-55 H 5-Ind S-b-57 SB Int. s-15 4MePh Me 1Me-5-Ind S-b-58 SA N-b-57 H 1 S-b-59 SB Int. s-17 2FPh Me 5-1 S-b-60 SA N-b-59 s S-b-61 SB Int. s-17 BRA6 2FPh Me 1 S-b-62 SA N-b-61 H 1 S-b-63 SB Int. s-17 2FPh Me 6-Qu C S-b-64 SA N-b-63 H 6-Qu C S-b-65 SB Int. s-19 3FPh Me 2-Nap C S-b-66 SA N-b-65 H 2-Nap C S-b-67 SB Int. s-19 BRA2 3FPh Me 5-Ind C S-b-68 SA N-b-67 H 5-Ind C S-b-69 SB Int. BRA6 3FPh Me 1 S-b-70 SA N-b-69 S-b-71 SB s-21 BRA3 4FPh Me 1 S-b-72 SA N-b-71 S-b-73 SB Int. s-21 BRA5 4FPh Me 5-1 S-b-74 SA N-b-73 H 5-1 Hldz C S-b-75 SS Int. s-21 BRA10 4FPh Me 3-Qu C S-b-76 SA N-b-75 H 3-Qu C S-b-77 SB Int. s-24 BRA1 cPen Me 2-Nap C S-b-78 SA N-b-77 H 2-Nap C S-b-79 SB Int. s-24 BRA2 cPen Me 5-Ind S-b-80 SA N-b-79 H 5-Ind C S-b-81 SB Int. s-24 BRA6 cPen Me 1 S-b-82 SA N-b-81 H 1 S-b-83 SB s-27 BRA3 cHex Et 1Me-5-Ind S-b-84 SA N-b-83 H 1 S-b-85 SB s-27 BRA5 cHex Et 5-1 S-b-86 SA N-b-85 H 5-1 S-b-87 SB Int, s-27 BRA12 cHex Et 6-Qu C S-b-88 SA N-b-87 H 6-Qu C S-b-89 SB Int. s-30 nPr Et 2-Nap C S-b-90 SA N-b-89 H 2-Nap C S-b-91 SB Int. s-30 BRA2 nPr Et 5-Ind C S-b-92 H 5-Ind C R>Table-S-B-3 LCMS Exp. Syn SM1 SM2 method Mass S-b-93 SB S-b-94 SA N-b-93 H 1 S-b-95 SB Int. s-33 BRA1 iPr Et 2-Nap C S-b-96 SA N-b-95 H 2-Nap S-b-97 SB Int. s-33 BRA3 iPr Et 1 S-b-98 SA N-b-97 H 1 S-b-99 SB Int. s-33 BRA5 iPr Et 5-1Hldz S-b-100 SA N-b-99 S-b-101 SB Int. s-36 BRA2 nBu Et 5-Ind C S-b-102 SA N-b-101 5-Ind C S-b-1 Int. s-36 BRA5 nBu Et 5-1 Hldz C S-b-104 SA N-b-1 H 5-1 HIdz S-b-105 SB Int. s-36 BRA11 nBu Et 6-Qu C S-b-1 SA N-b-1 H 6-Qu C S-b-107 SB Int. s-39 BRA1 iBu Me 2-Nap C377 S-b-108 SA N-b-107 +1 S-b-109 SB Int. s-39 BRA3 iBu Me S-b-110 SA N-b-109iBu H 1 S-b-111 SB Int. s-39 BRA5 iBu Me 5-1 S-b-112 SA N-b-111iBu H 5-1 S-b-113 SB Int. s-39 BRA6 iBu Me 1 S-b-114 SA N-b-113 H 1 S-b-115 SB Int. s-42 BRA1 PhEt Me 2-Nap C S-b-116 SA N-b-1 H 2-Nap C S-b-117 SB Int. s-42 BRA2 PhEt Me 5-Ind C S-b-118 SA N-b-117 H 5-Ind C S-b-119 SB Int. s-42 BRA3 PhEt Me 1 S-b-120 SA N-b-11 H 1 S-b-121 SB Int. s-45 BRA1 Et 2-Nap C S-b-122 SA N-b-12 2-Nap C S-b-123 SB Int. s-45 BRA5 4MeoBn Et 5-1 S-b-124 SA N-b-1234MeOBn H 5-1 HIdz C S-b-125 SB Int. s-45 BRA6 4MeOBn Et 1 S-b-126 SA N-b-1254MeOBn H 1 S-b-127 SB Int. s-48 BRA1 4FBn Et 2-Nap c S-b-128 SA N-b-12 H 2-Nap C S-b-129 SB Int. s-48 BRA2 4FBn Et 5-Ind C S-b-130 SA N-b-129 H 5-Ind C S-b-131 SB Int. s-48 BRA6 4FBn Et 1 S-b-132 SA N-b-13 H 1 S-b-133 SB Int. BRA3 2MeBn Et 1 S-b-134 SA N-b-133 H 1Me-5-Ind S-b-135 SB Int. s-51 BRA5 2MeBn Et 5-1 S-b-136 SA N-b-13 H 5-1 S-b-137 SB Int. 2MeBn Et 3-Qu C S-b-138 SA N-b-137 Rx-S<5O-Y Table-S-C-1 AR Exp. Syn SM1 SM2 Rx Y method Mass S-c-1 SB Ints-6 BRA1 4MeOPh Me 2-Nap S-c-2 SA S-c-1 H 2-Nap S-c-3 SB s-6 BRA2 Me 5-Ind S-c-4 SA S-c-3 H 5-Ind S-c-5 SB Int. s-6 BRA3 4MeOPh Me 1 S-c-6 SA S-c-5 H 1 S-c-7 SB Int. s-6 BRA4 4MeOPh Me 1Et-5-lnd S-c-8 SA S-c-7 S-c-9 SB Int. s-6 BRA5 4MeOPh Me 5-lHIdz S-c-10 SA S-c-9 H 5-lHIdz S-c-11 SB Int. s-6 BRA6 4MeOPh Me 1 S-c-12 SA S-c-11 H Me-5-1 S-c-13 SB Int. s-6 BRA7 4MeOPh Me 1 S-c-14 SA S-c-13 H 1 S-c-15 SB Int. s-6 BRA8 4MeOPh Me 2Me-5-2HIdz C S-c-16 SA S-c-15 H 2Me-5-2HIdz C S-c-17 SB Int. s-6 BRA9 4MeOPh Me 5-Bzt C S-c-18 SA S-c-17 5-Bzt C S-c-19 SB Int. s-6 BRA10 4MeOPh Me 3-Qu C S-c-20 SA S-c-19 H 3-Qu C S-c-21 SB Int. s-6 BRA11 4MeOPh Me 6-Qu C S-c-22 SA S-c-21 H 6-Qu C S-c-23 SB Int. s-6 BRA12 4MeOPh Me 6-IQ C S-c-24 SA S-c-23 H 6-IQ C S-c-25 SB Int. s-8 BRA1 2MeOPh Me 2-Nap C S-c-26 SA S-c-25 H 2-Nap C S-c-27 SB Int. s-8 BRA3 2MeOPh Me 1 S-c-28 SA S-c-27 H 1Me-5-Ind S-c-29 SB Int. s-8 BRA5 2MeOPh Me 5-1 S-c-30 SA S-c-29 H 5-1 S-c-31 SB Int. s-8 BRA10 2MeOPh Me 3-Qu'C S-c-32 SA S-c-31 H 3-Qu C S-c-33 SB Int. s-10 3MeOPh Me 2-Nap C S-c-34 SA S-c-33 H 2-Nap C S-c-35 SB Int. s-10 3MeOPh Me 5-Ind C S-c-36 SA S-c-35 H 5-Ind S-c-37 SB Int. s-10 3MeOPh Me 1 S-c-38 SA S-c-37 H 1 S-c-39 SB Int. s-10 3MeOPh Me 6-Qu C S-c-40 SA S-c-39 H 6-Qu C S-c-41 SB Int. s-12 BRA3 2MePh Me 1-Me-5-Ind S-c-42 SA S-c-41 H 1-Me-5-Ind C 388 388 S-c-43 SB Int. s-12 Me 5-1 S-c-44 SA S-c-43 H 5-1 S-c-45 SB Int. BRA6 2MePh Me 1-Me-5-1 S-c-46 SA S-c-45 H 1-Me-5-lHldz Rx Y Table-S-C-2 LCMS Exp. Syn SM1 SM2 Rx Y Y method Mass S-c-47 SB +1 S-c-48 SA N-c-47 H 1-Me-5-Ind C S-c-49 SB Int. BRA6 3MePh Me 1-Me-5-1HIdz S-c-50 SA N-c-49 H 1-Me-5-1 S-c-51 SB Int. s-14 BRA9 3MePh Me 5-Bzt C S-c-52 SA N-c-51 H 5-Bzt C S-c-53 SB Int. 4MePh Me 2-Nap C S-c-54 SA N-c-53 H 2-Na S-c-55 SB Int. s-16 BRA2 4MePh Me 5-lnd S-c-56 SA N-c-55 H 5-Ind C S-c-57 SB Int 4MePh Me 1 S-c-58 SA N-c-57 H 1Me-5-Ind S-c-59 SB Ints-18 BRA5 2FPh Me 5-1 Hldz C S-c-60 SA N-c-59 H 5-1 S-c-61 SB Int. s-18 BRA6 2FPh Me 1 S-c-62 SA N-c-61 H 1-Me-5-1 S-c-63 SB Int. 2FPh Me 6-Qu C ++ S-c-64 SA N-c-63 H 6-Qu C S-c-65 SB Int. s-20 BRA1 3FPh Me 2-Nap C S-c-66 SA N-c-65 H 2-Nap C S-c-67 SB Int. s-20 BRA2 3FPh Me 5-Ind C405 +1) S-c-68 SA N-c-67 H 5-Ind C S-c-69 SB Int. s-20 BRA6 3FPh Me 1 S-c-70 SA N-c-69 H I S-c-71 SB Int. s-22 BRA3 4FPh Me 1 S-c-72 SA N-c-71 H 1 S-c-73 SB Int. s-22 BRA5 4FPh Me 5-lHIdz S-c-74 SA N-c-73 H 5-1 S-c-75 SB Int. s-22 BRA10 4FPh Me 3-Qu C S-c-76 SA N-c-75 H 3-Qu C S-c-77 SB Int. s-25 BRA1 Et 2-Nap C S-c-78 SA N-c-77 H 2-Nap C377 S-c-79 SB Int. s-25 BRA2 cPen Et 5-Ind C S-c-80 SA N-c-79 H 5-Ind C S-c-81 SB Int. s-25 BRA6 cPen Et 1 S-c-82 SA N-c-81 H 1 S-c-83 SB Int, s-28 BRA3 cHex Et 1 S-c-84 SA N-c-83 H 1 S-c-85 SB Int, s-28 BRA5 cHex Et 5-1 S-c-86 SA N-c-85 H 5-1 S-c-87 SB Int, s-28 BRA12 Et 6-Qu C S-c-88 SA N-c-87 H 6-Qu C S-c-89 SB Int. s-31 BRA1 nPr Et 2-Nap C S-c-90 SA N-c-89 H 2-Nap C S-c-91 SB Int. s-31 BRA2 nPr Et S-c-92 SA N-c-91 H 5-Ind C AR LCMSTable-S-C-3 LCMS Exp. SM1 SM2 Rx Y Air method RTime Mass S-c-93 S-c-94 SA N-c-93 H 1 S-c-95 SB Int. s-34 BRA3 iPr Et S-c-96 SA N-c-95 S-c-97 SB Int. s-34 BRAS S-c-98 SA N-c-97 H 5-1 Hldz S-c-99 SB Int. s-34 BRA12 iPr Et 6-IQ S-c-100 SA N-c-99 iPr H 6-IQ C S-c-101 s-37 BRA1 nBu Et 2-Nap C S-c-102 SA N-c-101nBu H 2-Nap C S-c-103 Et 5-Ind C S-c-104 S-c-105 SB Int. s-37 BRA6 nBu Et 1 S-c-106 SA N-c-l S-c-107 SB Int. s-40 BiA1 t S-c-108 SA N-c-1 H 2-Nap C S-c-109 SB Int. s-40 BRA3 Et 1 S-c-110 SA N-c-1 H 1 S-c-111 SB Int. s-40 BRA5 iBu Et 5-1 S-c-112 SA N-c-l H 5-'1 S-c-113 SB Int. s-40 BRA6 iBu Et 1 S-c-114 SA N-c-l H I S-c-115 SB Int. s-43 BRA1 PhEt Et 2-Nap C S-c-116 SA N-c-l H 2-Nap C S-c-l s-43 BRA2 PhEt Et 5-Ind C S-c-118 SA N-c-117 H 5-Ind C S-c-119 SB Int. s-43 BRA6 PhEt Et 1 S-c-120 SA N-c-l H 1 S-c-121 SB Int. s-46 BRA1 4MeOBn Et 2-Nap C S-c-122 SA N-c-1214MeOBn H 2-Nap C429 +1) S-c-123 SB Int. s-46 BRA3 4MeOBn Et S-c-124 SA N-c-1234MeOBn H 1 S-c-125 SB Int. s-46 BRA5 4MeOBn Et 5-1 S-c-126 H 5-1 S-c-127 SB Int. s-49 BRA1 4FBn Et 2-Nap C S-c-128 SA N-c-127 H 2-Nap C S-c-129 SB Int. s-49 BRA2 4FBn Et 5-Ind C S-c-130 SA N-c-I H 5-Ind C S-c-131 SB Int. 4FBn Et 5-1 S-c-132 SA N-c-l H 5-1 Hldz C S-c-133 Int. s-52 BRA3 2MeBn Et 1 S-c-134 SA N-c-l H 1 S-c-135 SB Int. s-52 BRA6 2MeBn Et 1 S-c-136 SA N-c-135 H 1 S-c-137 SB Int. s-52 BRA11 2MeBn Et 6-Qu S-c-138 SA N-c-137 H 6-Qu C [Example S-d-1] Synthesis of ethyl 3-{4-[(4-methoxyphenyl)methylsulfinyl]-3-(naphthalen-2- yl) phenyl} propionate (Compound No. S-d-1) (Synthesis method SG) A solution of the compound of Example S-c-121 (130.9 mg) in dichloromethane (4 ml) was added with 3-chloroperoxybenzoic acid (60.0 mg, TCI), and stirred at room temperature for 1.5 hours. The reaction mixture was added with water (10 ml), extracted with dichloromethane (20 ml), and then washed with saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, chloroform : methanol = 30 : 1) to obtain the title compound (Compound No. S-d-1, 108. 7 mg).
[Example S-d-7] Synthesis of ethyl 3- {4- [ (4-methoxyphenyl) methylsulfonyl]-3- (naphthalen-2- yl) phenyl} propionate (Compound No. S-d-7) (Synthesis method SG) A solution of the compound of Example S-c-121 (53.1 mg) in dichloromethane (3 ml) was added with 3-chloroperoxybenzoic acid (74.5 mg, TCI), and stirred at room temperature for 5 hours. The reaction mixture was added with water (10 ml), extracted with dichloromethane (20 ml), and then washed with saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 4 : 1) to obtain the title compound (Compound No. S-d-7,48. 1 mg).
[Examples S-d-1 to S-d-36] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-S-D-1. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, and the starting compounds 1 are mentioned in the columns of"SM1". (0) Rx-S AR Table-S-D-1 Exp. Syn SM1 RS (O) n method Mass S-d-1 SG S-c-121 4MeOBnSO Et 2-Nap C473 +1) S-d-2 SA S-d-1 4MeOBnSO H 2-Nap C445 S-d-3 SG S-c-123 4MeOBnSO Et'1Me-5-Ind ++1 S-d-4 SA S-d-3 4MeOBnSO S-d-5 SG S-c-125 4MeOBnSO Et 5-1 Hldz C S-d-6 SA S-d-5 4MeOBnSO H 5-1 Hldz C +1 S-d-7 SG S-c-121 Et 2-Nap C +1 S-d-8 SA S-d-7 4MeOBnS02 H _ S-d-9 SG 5-c-123 S-d-10 SA S-d-9 4MeOBnS02 H 1 S-d-11 SG S-c-125 4MeOBnS02 Et 5-1 S-d-12 SA S-d-11 H 5-1 Hldz +1 S-d-l SG S-c-77 cPenSO Et 2-Nap +1) S-d-14 SA S-d-13 H 2-Nap S-d-15 S-c-79 cPenSO Et 5-Ind S-d-16 SA S-d-15 cPenSO H 5-Ind S-d-17 SG S-c-81 Et 1 S-d-18 SA S-d-17 H 1 S-d-19 SG S-c-77 cPenS02 Et 2-Nap +n S-d-20 SA S-d-19 H 2-Nap C409 +D S-d-21 SG cPenS02 Et 5-Ind S-d-22 SA S-d-21 cPenS02 H 5-Ind C S-d-23 SG S-c-81 cPenS02 Et S-d-24 SA S-d-23 cPenS02 H 1 S-d-25 SG S-c-101 nBuSO Et 2-Nap C S-d-26 SA S-d-25 nBuSO H 2-Nap C S-d-27 SG nBuSO Et 5-Ind +1 S-d-28 SA S-d-27 nBuSO H 5-Ind C S-d-29 SG S-c-105 nBuSO Et 1 S-d-30 SA S-d-29 nBuSO H 1Me-5-1HMz S-d-31 SG S-c-101 nBuS02 Et 2-Nap G S-d-32 SA S-d-31 nBuS02 H 2-Nap C S-d-33 SG S-c-103 Et 5-Ind C S-d-34 SA S-d-33 nBuS02 H 5-Ind S-d-35 nBuS02 Et 1 S-d-36 S-d-35 nBuS02 H 1 n-p Y[Reference Examples : Intermediates An-l to An-5] Synthesis of ethyl 3- [2-hydroxy-3- (naphthalen-2-yl) pyridin-5-yl] propionate (Intermediate Ah-1) A solution of the compound of Example P-42 (452 mg) in a mixture of ethyl acetate (5 ml) and methanol (2.5 ml) was added with 10% palladium/carbon (50 mg), and stirred at room temperature for 2 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure to obtain the title compound (Intermediate Ah-1, 321 mg). Mass (FAB): 322 (M++1).
Synthesis of ethyl 3- [3- (naphthalen-2-yl)-2- (trifluoromethanesulfonyl) pyridin-5- yl] propionate (IntermediateAn-l) According to the procedure described in the synthesis method of Intermediate Aa-1, Intermediate Ah-1 (310 mg) and trifluoromethanesulfonic anhydride (170, u 1) were reacted and treated to obtain the title compound (Intermediate An-1, 355 mg). Mass (FAB): 454 (M++1).
Typical examples of the reaction intermediates that can be obtained by reacting and treating corresponding starting compounds according to the method described above are shown below.
Intermediate An-2 : ethyl 3- [3- (lH-indol-5-yl)-2- (trifluoromethanesulfonyl) pyridin-5- yljpropionate Intermediate An-3: ethyl 3- [3- (1-methyl-lH-indol-5-yl)-2- (trifluoromethanesulfonyl) pyridin-5-yl] propionate Intermediate An-4: ethyl 3- [3- (lH-indazol-5-yl)-2- (trifluoromethanesulfonyl) pyridin-5-yl] propionate Intermediate An-5: ethyl 3- [3- (l-methyl-lH-indazol-5-yl)-2- (trifluoromethanesulfonyl) pyridin-5-yl] propionate [Examples Cn-1 to Cn-45] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds according to the methods described in Examples Ca-1 and Ca-2 are shown in Table-Cn-1.
In the table, the substances mentioned in the column of"SMI"correspond to reaction intermediates, and the substances mentioned in the column of"SM2" correspond to the boronic acid reagent used in Example Ca-l. The boronic acid reagents indicated with the symbols of"BRA (number) "in the columns of"SM2"are those mentioned in Table-Ba-1 and Table-Ba-2. R Rx /O Table-Cn-1 ...,.",. Exp. Rx Y AR SM1 SM2 _ Cn-1 Ph Et 2-Nap An-1 Cn-2 Ph H 2-Nap Cn-1-C Cn-3 Ph Et 5-Ind An-2 BRA14 C Cn-4 Ph H 5-Ind Cn-3-C Cn-5 Ph Et 1 An-3 BRA14 C -1) Cn-6 Ph H'I Cn-7 Ph Et 5-1 Hldz An-4 BRA14 C Cn-8 Ph H 5-1Hldz Cn-9 Ph Et 1 An-5 BRA14 C Cn-10 Ph H 1Me-5-1HMz Cn-11 4MeOPh H 2-Nap An-1 BRA19 C Cn-12 4MeOPh H 5-Ind An-2 BRA19 Cn-13 4MeOPh H 5-1 An-4 BRA19 Cn-14 H 1 An-5 BRA19 Cn-15 3MeOPh H 2-Nap An-1 BRA37 C Cn-16 2-Nap An-1 BRA38 C Cn-17 2MeOPh H 1Me-5-Ind An-3 BRA38 C Cn-18 2MeOPh H 1 An-5 BRA38 C Cn-19 2MePh H 2-Nap An-1 BRA59 C Cn-20 2MePh H 1Me-5-Ind An-3 BRA59 C Cn-21 2MePh H 1 An-5 BRA59 2 Cn-22 3MePh H 2-Nap An-1 BRA60 C Cn-23 3MePh H 5-lHldz An-4 B Cn-24 4MePh-H 2-Nap An-1 BRA29 C Cn-25 4MePh H 5-Ind An-2 BRA29 C357 Cn-26 4MePh H 1 An-3 BRA29 C Cn-27 4MePh H 5-lHldz An-4 BRA29 C Cn-28 4MePh H BRA29 372 Cn-29 4CF3Ph H 5-Ind An-2 BRA41 C Cn-30 4CF3Ph H 5-1 An-4 BRA41 C Cn-31 4CF3Ph H 1 An-5 BRA41 426 Cn-32 4CiPh H 5-Ind An-2 BRA30 C Cn-33 4CIPh H 1Me-5-Ind An-3 BRA30 391 Cn-34 4CIPh H 1Me-5-1Hldz_ An-5 BRA30 C Cn-35 2FPh H 2-Nap An-1 BRA32 C Cn-36 2FPh H 1Me-5-Ind An-3 BRA32 Cn-37 2FPh H 5-1 Hldz An-4 BRA32 C Cn-38 2FPh H 1 An-5 BRA32 C Cn-39 3FPh H 5-Ind An-2 BRA33 C Cn-40 3FPh H 5-lHldz An-4 BRA33 C Cn-41 3FPh H 1 An-5 BRASS Cn-42 4FPh H 2-Nap An-1 BRA34 C Cn-43 4FPh H 5-Ind An-2 BRA34 Cn-44 4FPh _ An-4 BRA34 Cn-45 4FPh H 1 An-5 BRA34 C [Reference Examples : Intermediates Int. n-1 to Int. n-115] Synthesis of methyl 3- (4-aminophenyl) propionate (Intermediate Int. n-1) (Synthesis method NL) A solution obtained beforehand by adding thionyl chloride (6.7 ml, WAKO) dropwise to methanol (50 ml) under ice cooling and mixing them was added dropwise with a solution of 4-aminohydrocinnamic acid (9.97 g, TCI) in methanol (50 ml) under ice cooling, stirred for 30 minutes, then warmed to room temperature, and further stirred for 16.5 hours. The reaction mixture was concentrated under reduced pressure, and then extracted with ethyl acetate (200 ml), and the organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate Int. n-1, 13.13 g).
Synthesis of methyl 3- (4-amino-3-bromophenyl) propionate (Intermediate Int. n-2) (Synthesis method NK) A solution of Intermediate Int. n-1 (9.93 g) in acetic acid (55 ml) was added with potassium bromide (6.60 g, WAKO) and sodium tungstenate (IV) dihydrate (18.23 g, WAKO), stirred for 5 minutes, then added dropwise with aqueous hydrogen peroxide (3.5 ml, WAKO) at 0°C over 5 minutes, warmed to room temperature, and then stirred for 1 hour. The reaction mixture was poured into 5% aqueous ammonia containing ice, thereby adjusted to pH of about 6, and then added with dichloromethane (200 ml) for extraction. The organic layer was washed successively with saturated aqueous ammonium chloride, saturated aqueous sodium hydrogencarbonate and saturated brine, and then dried, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 3 : 1) to obtain the title compound (Intermediate Int. n-2, 3.07 g).
Synthesis of methyl 3- (4-benzylamino-3-bromophenyl) propionate (Intermediate Int. n-3) (Synthesis method NC1) A solution of Intermediate Int. n-2 (10.97 g) in methanol (30 ml) was added with benzaldehyde (5.25 ml, TCI) and anhydrous sodium sulfate (6. 49 g, WAKO), and stirred at 60°C for 13 hours. The reaction mixture was added with sodium cyanotrihydoridoborate (2.73 g, WAKO), and further stirred for 5 hours. The reaction mixture was. concentrated under reduced pressure, and then extracted with dichloromethane (150 ml), and the organic layer was washed with saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 4 : 1) to obtain the title compound (Intermediate Int. n-3, 13.45 g).
Synthesis of methyl 3- [3-bromo- (4-fluorobenzylamino) phenyl] propionate (Intermediate Int. n-4) (Synthesis method NC2) A solution of Intermediate Int. n-2 (5.80 g) in dichloromethane (100 ml) was added with p-fluorobenzaldehyde (2. 83 ml, TCI), sodium triacetoxyborohydride (7.14 g, Ald) and acetic acid (1.4 ml), and stirred at room temperature for 19 hours.
The reaction mixture was extracted with dichloromethane (300 ml), and the organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 4 : 1) to obtain the title compound (Intermediate Int. n-4,7. 51 g).
Synthesis of methyl 3- [4-amino-3- (naphthalen-2-yl) pheny propionate (Intermediate Int. n-7) (Synthesis method NDl) A solution of the compound of Example N-a-1 (3.01 g) in a mixture of methanol (40 ml) and THF (20 ml) was added with 10% palladium/carbon (410.3 mg, Merck) and one drop of concentrated hydrochloric acid, and stirred at room temperature for 5 hours under hydrogen atmosphere. The reaction mixture was filtered, and the solvent of the filtrate was evaporated under reduced pressure.
The residue was added with ethyl acetate (200 ml), and washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and then dried, and the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate Int. n-7, 2.58 g).
Synthesis of methyl 3- [3-nitro-4- (piperazin-1-yl) phenyl] acrylate (Intermediate Int. n-19) (Synthesis method NJ) A solution of methoxycarbonylmethyl (triphenyl) phosphonium bromide (1.1 g, TCI) in THF (12.5 ml) was added with sodium hydride (115 mg, WAKO) under ice cooling, warmed to room temperature, then added dropwise with a solution of 3- nitro-4-(piperazin-1-yl) benzaldehyde (550.6 mg, MAYB) in THF (12.5 ml), and stirred at the same temperature for 16.5 hours. The reaction mixture was poured into brine (40 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane : ethyl acetate = 5 : 1) to obtain the title compound (Intermediate Int. n-19, 511 mg).
Synthesis of methyl 3- [3-amino-4- (pip erazin-1-yl) phenyl] propionate (Intermediate Int. n-20) (Synthesis method ND1) According to the procedure described in the synthesis method of Intermediate Int. n-7 (Synthesis method NDl) provided that the reaction was carried out in ethyl acetate for 13 hours, Intermediate Int. n-19 (505 mg) and 10% palladium/carbon (50 mg) were reacted and treated to obtain the title compound (Intermediate Int. n-20,658. 9 mg).
Synthesis of methyl 3- [3-bromo-4- (piperazin-1-yl) phenyl] propionate (Intermediate Int. n-21) (Synthesis method NI) A solution of hydrobromic acid (570, u 1) in methanol (2.3 ml) was added dropwise with a solution of Intermediate Int. n-20 (235 mg) in methanol (2.3 ml) over 10 minutes under ice cooling. This reaction mixture was added with an aqueous solution (250 A 1) of sodium nitrite (69 mg, WAKO). The reaction mixture was added dropwise with an aqueous solution (2.3 ml) of copper (II) bromide (222 mg, WAKO) heated to 50°C over 15 minutes, stirred for 4 hours at the same temperature, and then further stirred at room temperature for 12.5 hours. The reaction mixture was poured into aqueous sodium hydrogencarbonate (20 ml), and extracted with ethyl acetate (40 ml). The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by flash column chromatography (hexane: ethyl acetate = 4: 1) to obtain the title compound (Intermediate Int. n-21,89 mg).
Synthesis of methyl 4-fluoro-3-bromocinnamate (Intermediate Int. n-25) (Synthesis method NL) According to the procedure described in the synthesis method of Intermediate Int. n-1 (Synthesis method NL) provided that the reaction was carried out for 1 hour, 3-bromo-4-fluorocinnamic acid (3.30 g, LANC) and thionyl chloride (1.5 ml) were reacted and treated to obtain the title compound (Intermediate Int. n- 25, 3.47 g) Synthesis of methyl 3- [3-bromo-4- (piperidin-1-yl) phenyl] cinnamate (Intermediate Int. n-26) (Synthesis method NG) A solution of Intermediate Int. n-25 (136.4 mg) in DMSO (5 ml) was added with potassium carbonate (109.8 mg) and piperidine (84. 8 u 1, TCI), and stirred at 90°C for 15 hours. The reaction mixture was extracted with ethyl acetate (50 ml), and then the organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : isopropyl ether = 6 : 1) to obtain the title compound (Intermediate Int. n-26, 120.4 mg).
Synthesis of methyl 3- [3-bromo-4- (piperidin-1-yl) phenyl] propionate (Intermediate Int. n-27) (Synthesis method ND2) According to a procedure described in literature [D. J. Hart et al. , Journal of Organic Chemistry (J. Org. Chem.), 1987, vol. 52, p. 4665], a solution of Intermediate Int. n-26 (690.6 mg) in dimethoxyethane (100 ml) was added with p- toluenesulfonhydrazide (2.97g, TCI), and refluxed by heating at 110°C. Then, the reaction mixture was added dropwise with an aqueous solution (100 ml) of sodium acetate (2. 85 g, WAKO) over 2 hours, and further stirred for 1 hour. The reaction mixture was extracted with dichloromethane (450 ml), and the organic layer was washed with water, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 6 : 1) to obtain the title compound (Intermediate Int. n-27, 648.2 mg).
Synthesis of 3-bromo- (4-imidazol-1-yl) benzaldehyde (Intermediate Int. n-32) (Synthesis method NG) According to the procedure described in the synthesis method of Intermediate Int. n-26 (Synthesis method NG) provided that the reaction was performed for 20 hours, and the column chromatography was performed with chloroform : methanol = 100 : 1, 3-bromo-4-fluorobenzaldehyde (1 246 g, TCI), potassium carbonate (825. 1 mg) and imidazole (444 mg, TCI) were reacted and treated to obtain the title compound (Intermediate Int. n-32,986. 1 mg).
Synthesis of ethyl 3- [3-bromo- (4-imidazol-1-yl) phenyl] acrylate (Intermediate Int. n- 33) (Synthesis method NJ) A solution of Intermediate Int. n-32 (986. 1 mg) and ethyl diethylphosphonoacetate (705, u 1) in 1,2-dimethoxyethane (8 ml) was added with 60% sodium hydride (180.2 mg) under ice cooling, stirred for 10 minutes, then warmed to room temperature, and stirred for 1 hour. The reaction mixture was added with dichloromethane (60 ml) for extraction, and the organic layer was washed with saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, dichloromethane: methanol = 100: 1) to obtain the title compound (Intermediate Int. n-33,1. 00 g).
Synthesis of methyl 3- (4-cyclopentylaminophenyl) propionate (Intermediate Int. n- 38) (Synthesis method NC1) According to the procedure described in the synthesis method of Intermediate Int. n-3 provided that the reaction was carried out for 6 hours, Intermediate Int. n-1 (1.03 g), cyclopentanone (450, u 1, TCI), sodium triacetoxyborohydride (1.56 g) and acetic acid (350 u 1) were reacted and treated to obtain the title compound (Intermediate Int. n-37, 1.21 g).
Synthesis of methyl 3- (4-cyclopentylamino-3, 5-dibromophenyl) propionate (Intermediate Int. n-39) (Synthesis method NK) A solution of Intermediate Int. n-37 (1.21 g) in acetonitrile was warmed to 35°C, then added with N-bromosuccinimide (2.44 g, TCI), and stirred for 1 hour.
The reaction mixture was concentrated under reduced pressure, then added with ethyl acetate (150 ml), washed successively with aqueous sodium thiosulfate, saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 6: 1) to obtain the title compound (Intermediate Int. n-38, 1.41 g).
Synthesis of 2-bromopyridine-5-carbaldehyde (Intermediate Int. n-44) (Synthesis method NM) According to a procedure described in literature (Xin Wang et al., Tetrahedron. Lett. , 2000, vol. 41, p. 4335], a solution of 2, 5-dibromopyridine (3.17 g) in anhydrous diethyl ether (140 ml) was added dropwise with a 1.6 M solution of n- butyl lithium in hexane (11 ml) with cooling at-78°C under argon gas atmosphere over 5 minutes, and stirred for 20 minutes. This reaction mixture was added dropwise with dehydrated DMF (1 ml) over 3 minutes, stirred for 30 minutes, then warmed to room temperature, and further stirred for 1 hour. The reaction mixture was added with water (20 ml), and extracted with ethyl acetate (30 ml x 2). The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 6: 1) to obtain the title compound (Intermediate Int. n-44,1. 46 g).
Synthesis of ethyl 3- (2-bromopyridin-5-yl) acrylate (Intermediate Int. n-45) (Synthesis method NJ) According to the procedure described in the synthesis method of Intermediate n-7 provided that the reaction was carried out for 15 minutes, Intermediate Int. n-44 (1.45 g), ethyl diethylphosphonoacetate (2.1 ml) and 60% sodium hydride (355 mg) were reacted and treated to obtain the title compound (Intermediate Int. n-45,1. 87 g).
Synthesis of ethyl 3- [2- (piperidin-1-yl) pyridin-5-yl] acrylate (Intermediate Int. n-46) (Synthesis method NG) Intermediate Int. n-45 (565. 7 mg) was added with potassium carbonate (286.4 mg) and piperidine (3 ml), and stirred at 90°C for 21 hours. The reaction mixture was added with ethyl acetate (50 ml), washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 4 : 1) to obtain the title compound (Intermediate Int. n-46, 165.9 mg).
Synthesis of ethyl 3-[2-(piperidin-1-yl) pyridin-5-yl] propionate (Intermediate Int. n- 47) (Synthesis method ND1) According to the procedure described in the synthesis method of Intermediate Int. n-7 with the modifications that the reaction was carried out for 1 hour, and the purification was performed by column chromatography (Quad, hexane: ethyl acetate = 6: 1), Intermediate Int. n-46 (392 mg) and 10% palladium/carbon (30 mg) were reacted and treated to obtain the title compound (Intermediate Int. n-47 246 mg).
Synthesis of ethyl 3- [3-bromo-2- (piperidin-l-yl) pyridin-3-yl] propionate (Intermediate Int. n-48) (Synthesis method NK2) A solution of Intermediate Int. n-47 (242 mg) in acetonitrile was added with bromine (84 u 1), and stirred at 40°C for 1 hour. The reaction mixture was concentrated under reduced pressure, then added with ethyl acetate (50 ml), washed successively with aqueous sodium thiosulfate, saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 6 : 1) to obtain the title compound (Intermediate Int. n-48,224 mg).
Synthesis of 2-benzylaminopyridine-5-carbaldehyde (Intermediate Int. n-59) (Synthesis method NG) Intermediate Int. n-44 (102.0 mg) was added with benzylamine (1 ml, TCI), and stirred at 120°C for 39 hours. The reaction mixture was added with ethyl acetate (50 ml), washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 4 : 1) to obtain the title compound (Intermediate Int. n-59,58. 3 mg).
Synthesis of 2-benzylamino-3-bromopyridine-5-carbaldehyde (Intermediate Int. n- 60) (Synthesis method NK) A solution of Intermediate Int. n-59 (56.8 mg) in acetonitrile was added with N-bromosuccinimide (134 mg), and stirred at room temperature for 14 hours.
The reaction mixture was concentrated under reduced pressure, then added with ethyl acetate (50 ml), washed successively with aqueous sodium thiosulfate, saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 4: 1) to obtain the title compound (Intermediate Int. n-60,50 mg).
Synthesis of ethyl 3- (2-benzylamino-3-bromopyridin-5-yl) acrylate (Intermediate Int. n-61) (Synthesis method NJ) According to the procedure described in the synthesis method of Intermediate Int. n-7 provided that the reaction was carried out for 30 minutes, Intermediate Int. n-60 (49.1 g), ethyl diethylphosphonoacetate (92, u 1) and 60% sodium hydride (30 mg) were reacted and treated to obtain the title compound (Intermediate Int. n-61, 28 mg).
Synthesis of ethyl 3- (2-benzylamino-3-bromopyridin-5-yl) propionate (Intermediate Int. n-62) (Synthesis method ND2) According to the procedure described in the synthesis method of Intermediate Int. n-27 provided that the reaction was carried out for 4 hours, Intermediate Int. n-60 (49.1 mg), p-toluenesulfonhydrazide (320.6 mg) and sodium acetate (412.4 mg) were reacted and treated to obtain the title compound (Intermediate Int. n-62,38. 9 mg).
Synthesis of methyl 3- (4-amino-3-bromo-5-nitrophenyl) propionate (Intermediate Int. n-76) (Synthesis method NM) A solution obtained by adding potassium nitrate (1.10 g) to a solution of Intermediate Int. n-2 (2.57 g) in acetic anhydride (20 ml) under ice cooling and stirring them for 10 minutes was added dropwise with concentrated sulfuric acid (700 u 1) over 10 minutes. The reaction mixture was stirred for 10 minutes at the same temperature, then warmed to room temperature, and further stirred for 30 minutes. The reaction mixture was poured into 1 N aqueous sodium hydroxide (250 ml) containing ice, and extracted with isopropyl ether (200 ml x 2). The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 3 : 1) to obtain the title compound (Intermediate Int. n-76,0. 72 g).
Typical examples of the intermediates for synthesizing the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table-Int. N-1 to Table-Int. N-8. In the tables, the intermediate numbers"Int. n- (number)" are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of"SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Further, the compounds indicated as"Single"in the columns of"Single or Double"in the tables are compound in which two of the carbon atoms binding the benzene ring and carbonyl group in the compounds are bound with a single bond, and those indicated as"Double"in the same are compounds in which two of the carbon atoms binding the benzene ring and carbonyl group in the compounds are bound with a double bond. The aldehydes and ketones used for the synthesis of the compounds are mentioned in Table-Carb, and amines used for the same are mentioned in Table-AMN.
Table-Carb Reagent or Ketone Manufacture CH01 HCHO CH02 CH3CHO CH03 CH3CH2CHO TCI CH04 nPrCHO TCI CH05 Acetone CH06 nBuCHO TCI CH07 iPrCHO TCI CH08 BnCHO TCI CH09 4FBnCHO TCI CH010 2FBnCHO TCI CHO11 3FBnCHO TCI CHO12 2CIBnCHO CH013 CHO14 2, 3DFBnCHO TCI CH015 3, 4DFBnCHO TCI CH016 CH017 2CF3BnCHO TCI CH018 2, 3DCIBnCHO TCI CH019 2-ThiofeneCHO (2-TFCHO) TCI CH020 3-ThiofeneCHO (3-TFCHO) CH021 2-FuranCHO (2-FRCHO) TCI CHO22 Cyclopentanone CH023 Cyclohexanone CH024 2 (Me) cHexanone TCI CHO25 2-lndanone AldehydeTable-AMN Reagent Amine AMN1 CNN n AMN2 AMN3 AMN4 AMN5 CNH TCI _, 'f'MU AMN6 Cz, N AMN7 4, AMN8 EtMeNH Aldrich AMN9 Et2NH Aldrich AMN10 nPrMeNH Aldrich AMN11 iPrMeNH Aldrich AMN12 nBuMeNH Aldrich AMN13 nBuEtNH Aldrich AMN14 iBuMeNH Aldrich AMN15 4MeBnNH2 Aldrich AMN16 3MeBnNH2 Aldrich AMN17 2MeBnNH2 Aldrich AMN18 AMN19 3FBnNH2 Aldrich AMN20 2FBnNH2 Aldrich AMN21 3MeOBnNH2 Aldrich AMN22 4MeOBnNH2 Aldrich AMN23 2MeOBnNH2 Aldrich AMN24 4CF3BnNH2 Aldrich AMN25 2EtOBnNH2 Atdrich AMN26 3iPrOBnNH2 Sigma-Aldrich AMN27 3, Rz-N 0 Table-Int. Exp. Syn SM1 SM2 Rz method RTime Mass Int. n-5 NC2 Int. n-2 CHO10 2FBn 366 Int. Int. n-2 CHO11 3FBn C 366 (M+) Int. Int. n-2 CH02 Et C Int. n-13 NC2 Int. n-2 CH03 nPr D 5. 02 300 (M+) Int. n-14 NC2 Int. n-2 CH05 iPr D 538 341 (M+) Int. n-15 NC2 Intn-2 CH07 iBu D 5. 50 400 (M+) Int. n-16 NC2 Irtn-2 CH022 open C Int. n-17 Int. n-2 CH023 f Intn-18 NC2 Int. 2 (Me) cHex C - Han Table-Int. N-2 AR Exp. Syn SM1 AR LEMS method RTime Mass Int. n-8 ND1 N-a-3 5-Ind C Int. n-9 ND1 N-a-5 1Me-5-Ind Intn-10 ND1 N-a-7 5-lldz Intn-11 ND1 SUD Rs---fCOOMe Table-Int. Exp. Syn. Rs G Single Double Mass Int. NJ N02 Double A 3. 91 293 (M++1) L Intn-23 A 2. 97 265 (M Int. NI A 4. 31 328 (M+) Rz Corme Table-Int. N-4 Exp. Syn SM1 RzRyN Single or Double method RTime Mass Intn-28 NC2 Int. n-25 A 6. 54 338 (M) v__i ! N A 6. 01 342 (M++1) Intn-30 NC2 Intn-25 A 6. 29 340 (M++1) tntn-31 n-30 Single A 6. 12 342 (M++1) Intn-33 NC2 Int. n-32 307 (M+) Int. n-35 NC2 Intn-32 306 (M+) tntn-36 Intn-25 CN A 5. 60 310 Intn-37 NC2 Intn-32 0 U N-y-CHO Table-Int. N-5 Exp. Syn SM1 RzRyN LCMS method Int. n-25 N 351 (M+) Int. n-34 NC2 z Rz-HNnX O HorBr Table-Int. N-6 Exp. Syn SM1 SM2 Rz Z'H or Br method Int. n-40 NC1 Int. nPr H H C Intn-41 NK Intn-40 Br Br C Intn-42 H H C Intn-43 NK Intn-42 O-Et \/ Table-Int. N-7 Br Exp. Syn RzRyN method RTime Mass Intn-48 Intn-49 NG Intn-50 NG 4 (Me) cHex C Int. n-51 NG N c 343 (M+) Int. n-52 NG cHep C 355 t Exp. Syn Rz Ry method Mass Intn-53 NG Et Me C Intn-54 NG Et Et C Intn-55 NG nPr Me C Intn-56 NG Me C Intn-57 NG nBu Me C Intn-58 NG iBu Me C Int. n-63 NG 4MeBn H C Int. n-64 NG 3MeBn H C Intn-65 NG 2MeBn H C Intn-66 NG 4FBn H C Intn-67 NG 3FBn H C Intn-68 NG 2FBn H C Intn-69 NG 4MeOPh H C Int. n-70 NG 3MeOPh H C Int. n-71 NG 2MeOPh H C Int. n-72 NG 4CF3Ph H C Int. n-73 NG 2EtOPh H C Intn-74 NG 3iPrOPh H C Intn-75 NG 3, 5DFPh H C 02N Rz N nit Table-Int. LCMS Exp. Syn SM1 SM2 Rz Ru _ Intn-77 NC2 Int. n-76 CH022 epen Int. n-78 NC2 Intn-76 CH03 nPr H C Int. n-79 NC2 Intn-76 CH05 iPr H C Int. n-80 NC2 Intn-76 CH025 2-Indane H C Int. n-81 NC2 Intn-76 H C Intn-82 Intn-76 CH024 2 (Me) cHex H C Int. n-83 NC1 Intn-77 CHO1 cPen Me C Int. n-84 NC1 tnt. n-78 nPr Me C ! Me C Int. n-86 NC1 Intn-80 CHO1 2-lndane 433 (M+) Int. n-87 N01 CH01 cHex Me C Int. n-88 NC1 Intn-82 (Me) cHex Me C Intn-89 Bn H C Intn-90 NC1 Intn-76 CH09 4FBn H C Int. NC2 Intn-76 CHO10 2FBn H H Intn-92 NC2 Intn-76 CH011 3FBn H G Int. n-93 NC2 Int. n-76 CH014 2, 3DFBn H C Intn-94 NC2 Int. n-76 CH015 3, 4DFBn H C Int. n-95 NC2 CH016 4PhBn H C Intn-96 CH017 2CF3Bn H C Int. n-97 NC2 Intn-76 CH019 2-TF H C Intn-98 NC2 Int. n-76 CH020 3-TF H C Int. n-99 NC2 Intn-76 CH021 2-FR H C Int. n-100 n-89 CH01 Bn Me C Int. n-90 CH01 4FBn Me Int. Me C Intn-103 3FBn Me Int. n-104 NC1 Intn-93 2, 3DFBn Me C Int. NC1 Intn-94 3, 4DFBn Me C Int. n-106 NC1 Intn-95 Me C Int. Intn-96 CH01 2CF3. Me C Int. n-108 NC1 Intn-97 2-TF Me C Int. n-109 NC1 Int. 3-TF Me C Int. n-110 NC1 n-99 CHO1 2-FR Me C Exp. Syn SM1 SM2 RzRyN LCMS method Mass Int. n-111 NM Intn-21 357 (M) Int. n-112 NM Int. n-24 CN 373 (M+) Int. Intn-114 NM Intn-29' 385 (M+) M+) Int. N [Example N-a-l] Synthesis of methyl 3- [4-benzylamino-3- (naphthalen-2-yl) phenyl] propionate (Compound No. N-a-1) (Synthesis method NBl) A solution of Intermediate n-3 (8.18 g) in toluene (60 ml) was added with 2- naphthaleneboronic acid (5.04 g, TCI), 2 M aqueous sodium carbonate (21.6 ml), methanol (24 ml) and tetrakistriphenylphosphine palladium (0) (henceforth abbreviated as" (Ph3P) 4Pd", 1.94 g, Nacalai Tesque), and stirred at 90°C for 15 hours. The reaction mixture was added with ethyl acetate (300 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane: ethyl acetate = 3 : 1) to obtain the title compound (Compound No. N-a-l, 5.70 g).
[Example N-a-2] Synthesis of 3- [4-benzylamino-3- (naphthalen-2-yl) phenyl] propionic acid (Compound No. N-a-2) (Synthesis method NA) A solution of the compound of Example N-a-1 (51 mg) in methanol (5.0 ml) was added with 2 N aqueous sodium hydroxide (130 u 1), and stirred at 60°C for 2 hours. The reaction mixture was concentrated under reduced pressure, then neutralized with 5% aqueous hydrochloric acid under ice cooling, and then extracted with ethyl acetate (30 ml). The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Compound No. N-a-2,47 mg).
[Example N-a-25] Synthesis of methyl 3- [4- (N-benzyl-N-methylamino)-3- (naphthalen-2- yl) phenyl] propionate (Compound No. N-a-25) (Synthesis method NC1) According to the procedure described in the synthesis method of Intermediate n-3 provided that the reaction was carried out for 5 hours, the compound of Example N-a-1 (234.2 mg), 30% aqueous solution of formaldehyde (208. 8 u 1, WAKO) and sodium cyanotrihydoridoborate (140.9 mg) were reacted and treated to obtain the title compound (Compound No. N-a-25,176. 3 mg).
[Example N-A-137] Synthesis of methyl 3- {3- (l-methyl-lH-indol-5-yl)-4- [N- (l- phenylethyl) amino] phenyl} propionate (Compound No. N-a-137) (Synthesis method NE 1) According to a procedure described in literature [Shin-Shyong Tseng et al., Journal of Organic Chemistry (J. Org. Chem. ), 1979, vol. 44, p. 4113], a solution of Intermediate n-9 (630. 7 mg) in methylene chloride (10 ml) was added with triethylamine (405 u 1, Kokusan Chemical), cooled to-78°C, then added dropwise with trifluoromethanesulfonyl chloride (426, u 1, TCI), and stirred for 1.5 hours.
The reaction mixture was poured into ice water (10 ml), and added with dichloromethane (30 ml) for extraction. The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure to obtain a crude product. A solution of the obtained crude product in DMF (15 ml) was added with potassium carbonate (394.2 mg) and (1- bromoethyl) benzene (386. 4, u 1, TCI), and stirred at room temperature for 13 hours.
The reaction mixture was extracted with ethyl acetate (100 ml), and the organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 4 : 1) to obtain the title compound (Compound No. N-a-137,310. 3 mg).
[Example N-a-141] Synthesis of methyl 3- [3- (l-methyl-lH-indol-5-yl)-4- {N- [2- (4- fluorophenyl) ethyl] amino} phenyl] propionate (Compound No. N-a-141) (Synthesis method NE2) A solution of Intermediate n-9 (210.1 mg) in methylene chloride (10 ml) was added with triethylamine (135 u 1, Kokusan Chemical), cooled to-78°C, then added dropwise with trifluoromethanesulfonyl chloride (143 u 1, TCI), and stirred for 1.5 hours. The reaction mixture was poured into ice water (10 ml), and added with dichloromethane (15 ml) for extraction. The organic layer was washed with saturated brine, and dried, and then the solvent was evaporated under reduced pressure to obtain a crude product. A solution of the obtained crude product in anhydrous DMF (15 ml) was added with triphenylphosphine (485.9 g, WAKO), di-t- butyl azodicarboxylate (299.8 mg, Ald) and 4-fluorophenylethyl alcohol (357 u 1, TCI), and stirred at room temperature for 12 hours. The reaction mixture was added with water (10 ml) and ethyl acetate (10 ml) for extraction, and the organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride, and saturated brine, and dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 4 : 1) to obtain the title compound (Compound No. N-a-141,63. 5 mg).
[Example N-a-143] Synthesis of methyl 3- [4- (N-acetyl-N-benzylamino)-3- (1-methyl-1H-indol-5- yl) phenyl] propionate (Compound No. N-a-143) (Synthesis method NF) A solution of Compound No. N-a-5 (32 mg) in methylene chloride (3 ml) was added with pyridine (49. 6 u 1, TCI) and acetyl chloride (50 u 1, TCI), and stirred for 13 hours. The reaction mixture was added with water (1 ml), and the solvent was evaporated. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 4: 1) to obtain the title compound (Compound No. N-a-143, 20.3 mg).
[Example N-a-153] Synthesis of methyl 3- [4-benzoylamino-3- (l-methyl-lH-indol-5-yl) phenyl] propionate (Compound No. N-a-153) (Synthesis method NF) According to the procedure described in the synthesis method of the compound of Example N-a-143 provided that the reaction was carried out for 16 hours, Intermediate Int. n-9 (26.5 mg), pyridine (23. 8 u 1) and benzoyl chloride (30 , u 1, WAKO) were reacted and treated to obtain the title compound (Compound No.
N-a-153,18. 4 mg).
[Examples N-a-1 to N-a-166] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-A-1 to Table-N-A-4. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of "Syn"with symbols, the starting compounds 1 are mentioned in the columns of "SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Zx 'nay Table-N-A-1 Exp. Syn SM1 Rz Ry Y Zx AU method Mass N-a-1 NB1 Int. n-3 BRN1 Bn H Me 2-Nap C +1) N-a-2 NA N-a-I H H H 2-Nap C N-a-3 NB1 Int. n-3 BRN2 Bn H H 5-lInd N-a-4 NA N-a-3 H H H N-a-5 NB1 Int. n-3 BRN3 Bn H Me H 1Me-5-Ind N-a-6 NA N-a-5Bn H H 1 385 (milz N-a-7 NB1 Int. n-3 BRN4 Bn H Me H 1Et-5-Ind N-a-8 NA N-a-7Bn H H H 1 +1) N-a-9 NB1 Int. n-3 BRN5 Bn H Me H 386 (M'++1) N-a-10 NA N-an H H H 5-1 N-a-I NB1 Int. n-3 BRN6 Bn H Me H 1 N-a-12 NA N-an H H N-a-13 NB1 Int. n-3 BRN7 Bn H Me H 1 N-a-14 NA N-an H H H 1Et-5-lHIdz N-a-15 Int. n-3 BRN8 H Me H 2Me-a-2HMz +1) N-a-16 NA N-an H H H 2Me-5-2HIdz N-a-17 NB1 Int. n-3 BRN9 Bn H Me H 5-Bzt c N-a-18 NA N-a-17 H 5-Bzt N-a-19 Int. n-3 BRN10 Bn H Me H 3-Qu c N-a-20 NA N-an H H H 3-Qu C N-a-21 NU1 Int. n-3 BRNH H Me N 397 (M++1) N-a-22 NA N-an H H H 6-Qu N-a-23 NB1 BRN12 Bn H Me H 6-IQ N-a-24 NA N-a-23 H N 6-IQ C N-a-25 NC1 N-a-1 CH01 Bn Me Me H 2-Nap C N-a26 Me H H 2-Nap C N-a-27 NC1 Et Me H 2-Nap C N-a-28 NA N-a-27 Et H H 2-Nap N-a-29 NC1 N-a-3 CH01 Bn Me Me H 5-1 N-a-30 NA N-FBn Me H H 5-7Ind N-a-31 NC1 N-a-5 CHO1 Bn Me Me H 1Me-5-Ind N-a-32 NA N-a-31 H H 1 N-a-33 NB1 Int. n-4 BRA1 4FBn H Me H 2-Nap C414 N-a-34 NA N-a-33 H H H 2-Nap C N-a-35 NB1 Int. n-4 BRA2 4FBn H Me H 5-1 D 5. 20 403 (M++1) N-a-36 NA N-a-354FBn H H H 5-1 D 4. 73 389 (M*+1) N-a-37 NB1 Int. n-4 BRA3 4FBn H Me H 1Me-5-Ind D 5. 51 417 (M++1) N-a-38 NA N-a-37 H H H D 4. 78 403 (M+D N-a-39 NB1 Int. n-4 BRA5 4FBn H Me H 5-1 D 4. 60 404 (M++1) N-a-40 NA N-a-39 H H H 5-1 N-a-41 NB1 Int. n-4 BRA6 4FBn H Me H I A 4. 85 418 (M+D N-a-42 NA N-a-41 H H H 1 A 4. 14 404 (M++1) N-a-43 NB1 Int. n-4 BRA10 4FBn H Me H 3-Qu D 4. 72 415 (M++1) N-a-44 NA N-a-43 H H H ARTable-N-A-2 LCMS Exp. Syn SM1 SM2 Rz Ry method Mass N-a-45 NC2 N-a-35 CH01 4FBn Me Me D 4. 17 417 (M++1) N-a-46 NA N-a-45 Me H H 5-Ind D 3. 38 403 M++1) N-a-47 NC2 N-a-37 CH01 4FBn Me Me H 1Me-5-Ind N-a-48 NA N-a-47 Me H H 1 N-a-49 NC2 N-a-41 CH01 4FBn Me Me H 1 N-a-50 NA N-a-49 Me H H 1 N-a-51 NC2 N-a-37 CH02 4FBn Et Me H 1 N-a-52 NA N-a-51 Et H H 1 N-a-53 NC2 N-a-39 CH02 4FBn Et Me H 5-lIdz N-a-54 NA N-a-53 Et H H 5-1 N-a-55 NB1 H Me H 2-Nap C N-a-56 NA N-a-55 H H H 2-Nap C N-a-57 NB1 Int. n-5 H Me H I N-a-58 NA N-a-57 H H H 1 N-a-59 NB1 Int. n-5 H Me H 1 N-a-60 NA N-a-59 H H H 1 N-a-61 NC2 N-a-59 CH01 2FBn Me Me H 1 N-a-62 NA N-a-61 Me H H 1 N-a-63 NB1 Int. n-6 H Me H 2-Nap C N-a-64 NA N-a-63 H H 2-Nap C N-a-65 NB1 Intn-6 3FBn H Me H 5-lInd N-a-66 NA N-a-65 H H H 5-1 N-a-67 NB Int. n-6 H Me H 1 N-a-68 NA N-a-67 H H H 1 N-a-69 NC2 N-a-67 CH01 3FBn Me Me H 1 N-a-70 NA N-a-69 H H 1 N-a-71 NC1 Int. n-7 CHO12 2CIBn H Me H 2-Nap C N-a-72 NA N-a-71 2CIBn H H H 2-Nap C N-a-73 NC1 Int. n-7 CHO13 H Me H 2-Nap C N-a-74 NA N-a-73 H H H 2-Nap C N-a-75 NC1 Int. n-7 CH014 2, 3DFBn H Me H 2-Nap C N-a-76 NA N-a-75 3DFBn H H H 2-Nap C418 +1) N-a-77 NC1 Int. n-7 CH021 2-FR H Me H 2-Nap C N-a-78 NA N-a-77 H H H 2-Nap C N-a-79 NC1 Int. n-7 CH020 3-TF H Me H 2-Nap C N-a-80 NA N-a-79 H H H 2-Nap C N-a-81 NC1 Int. n-7 CH017 2CF3Bn H Me H 2-Nap C N-a-82 NA N-a-80 H H H 2-Nap C N-a-83 NC1 Int. n-8 CH012 2CIBn H Me H 5-1Ind N-a-84 NA N-a-80 H H H 5-lInd N-a-85 NC2 N-a-80 CH01 Me Me H 5-1 N-a-86 NA N-a-85 2CIBn Me H H 5-1 N-a-87 NC1 Int. n-8 CH014 2, 3DFBn H Me H 5-1Ind C N-a-88 NA N-a-87 H H H 5-1 N-a-89 NC1 Int. n-8 CH016 4PhBn Me H 5-11nd N-a-90 NA N-a-89 H H H 5-1Ind Y Zx AR LCMSTable-N-A-3 Exp. Syn SM1 SM2 Rz Ry AR _ Mass N-a-91 NC1 Int. n-8 CH019 2-TF H Me H 5-Ind C391 N-a-92 NA N-a-91 H H H 5-Ind C N-a-93 NC1 Int. n-8 CH017 2CF3Bn H Me H 5-Ind C N-a-94 NA N-a-93 H H 5-Ind C N-a-95 NC1 Int. n-8 CH018 2, 3DCIBn H Me H 5-Ind C N-a-96 NA N-a-71 H H H 5-Ind C N-a-97 NC1 Int. H Me H 1Me-5-Ind N-a-98 NA N-a-97 H H H 1 N-a-99 NC1 Int. n-9 CH015 3, 4DFBn H Me H 1Me-5-lnd N-a-100 NA N-a-99 H H H 1Me-5-Ind N-a-101 n-9 CH016 4PhBn H Me H 1Me-5-Ind N-a-102 NA N-a-1 H H H 1 N-a-103 NC1 Int. n-9 CH021 2-FR H Me H 1 N-a-104 NA N-a-103 H H H 1 N-a-105 Int. n-9 CH020 3-TF H-Me N-a-106 NA N-a-105 H H H 1 N-a-107 Int. n-9 CH018 2, 3DCIBn H Me H 1 N-a-108 NA N-a-107, H H 1 1Me-5-Ind N-a-109 NC1 Int. n-10 2BrBn H Me H 5-1 N-a-110 NA N-a-109 H H H 5-1 N-a-111 Int. n-10 4DFBn H Me H 5-1 N-a-112 NA N-a-1113, 4DFBn H H H 5-1 N-a-113 NC2 N-a-111 CH01, 4DFBn Me Me H 5-1 N-a-114 NA N-a-113 4DFBn Me H 5-1 N-a-115 NC1 Int. n-10 CH021 2-FR H Me H 5-1 N-a-116 NA N-a-l H H H 5-1 N-a-117 Int. n-10 CH020 3-TF H Me H 5-1 N-a-118 NA N-a-116 H H H 5-1HIdz N-a-11 Int. n-10 H 5-1 N-a-120 NA N-a-120 H H H 5-1Hldz. -a-12 Int. n-10 CHO 2, 3DCIB H Me H 1 N-a-122 NA N-a-122 H H H 1 N-a-123 H Me H 1 N-a-124 NA N-a-123 H H 1 Me-5-1 N-a-l Me Me H N-a-126 NA N-a-125 H 1 Me-5-1 N-a-127 NC1 Int. n-l 3DFBn H Me H 1 N-a-128 NA N-a-127 3DFBn H H H 1 -a-12 Int. n-11 4DFBn H Me H 1 N-a-130 NA N-a-W 4DFBn H H H 1 N-a-131 Int. n-11 4PhBn H Me H N-a-132 NA N-a-131 H H H 1 1) N-a-133 Int. n-11 CH019 2-TF H Me H N-a-134 NA N-a-133 H H H 1 N-a-135 NC1 Int. 2CF3Bn H Me H 1Me-5-1Hld2 N-a-136 H 1 LCMSTable-N-A-4 Loms Exp. Syn SM2 Rz Ry Y Zx AR . Mars N-a-137 n-9 dOH Me H 1 '' 413 (M+1 N-a-138 NA N-a-13 H H 1 399 N-a-139 Me H 1 D 5. 06 L N-a-140 NA N-a-139 Cß H H 1 Me-5-1 D 4. 30 400 (M +1 N-a-141 NE2 Int. n-11 2 (4FPh) EtOH H Me H H D 5. 08 432 (M++1) N-a-142 NA N-a-14 (4FPh) Et H H 1 D 4. 25 418 (M++1) N-a-143 NF N-a-5 AcCI Bn Ac Me H 1Me-5-1HIdz N-a-144 NA N-a-143 Ac H H 1 N-a-145 NF N-a-5 PhCOCI Bn PhC Me H 1 N-a-146 NA N-a-145Bn (O) H H XMe-5-lnd C N-a-147 NF N-a-5 MeOCH2COCl Bn MeOCH2C (O) Me H N-a-148 NA N-a-14, H H 1 N-a-149 NF N-a-5 MeOCOCI Bn MeOC (O) Me H 1 N-a-150 NA N-a-149Bn (O) H H 1 N-a-151 NF N-a-5 PhOCOCI Bn PhOC Me H 1Me-5-Ind N-a-152 NA N-a-l H H 1Me-5-Ind N-a-153 NF N-a-5 NMe2COCl Bn Me2NC Me H 1 N-a-154 NA N-a-153 H H N-a-155 NF N-a-11 Bn Ac Me H N-a-156 NA N-a-155 H H 1 N-a-157 N-a-5 AGCI 4FBn Ac Me H 1 N-a-158 NA N-a-157 Ac H H 1 N-a-159 N-a-5 Meoomcoct 4FBn MeOCH2C (o) Me H 1 N-a-160 NA N-a-l H 1Me-5-Ind N-a-161 NF N-a-5 (O) Me H 1Me-5-Ind N-a-162 NA N-a-1614FBn (O) H H 1 N-a-163 4FBn Ac H 1 N-a-164 NA N-a-l Ac H H 1 N-a-165 NF N-a-11 4FBn MeOC (O) Me H 1 N-a-166 (O) H H 1 [Example N-b-1] Synthesis of methyl 3- [4- (N-methylamino)-3- (naphthalen-2-yl) phenyllpropionate (Compound No. N-b-1) (Synthesis method ND1) According to the procedure described in the synthesis method of Intermediate Int. n-7 (Synthesis method ND1) provided that the reaction was carried out for 2 hours, the compound of Example N-a-25 (100.3 mg) and 10% palladium/carbon (10.2 mg) were reacted and treated to obtain the title compound (Compound No. N-b-1, 89.7 mg).
[Example N-b-35] Synthesis of methyl 3- [4- (N-ethylamino)-3- (naphthalen-2-yl) phenyl] propionate (Compound No. N-b-35) (Synthesis method NBI) According to the procedure described in the synthesis method of the compound of Example N-a-1 (Synthesis method NB1) provided that the reaction was carried out for 17 hours, Intermediate n-12 (99.87 mg), 2-naphthaleneboronic acid (87. 3 mg), 2 M aqueous sodium carbonate (350, u 1) and (Ph3P) 4Pd (59.6 mg) were reacted and treated to obtain the title compound (Compound No. N-b-35,103. 5 mg).
Example N-b-79] Synthesis of methyl 3- [4- (N-n-butylamino) -3- (naphthalen-2-yl) phenyl] propionate (Compound No. N-b-79) (Synthesis method NC2) According to the procedure described in the synthesis method of Intermediate n-3 provided that the reaction was carried out for 13 hours, Intermediate n-7 (164.7 mg) and n-butylaldehyde (38.5 u 1, KANTO), sodium triacetoxyborohydride (138.6 mg) and acetic acid (75 u 1) were reacted and treated to obtain the title compound (Compound No. N-b-79,161. 3 mg).
[Example N-b-183] Synthesis of methyl 3- [4- (N-acetyl-N-methylamino)-3- (naphthalen-2- yl) phenyl] propionate (Compound No. N-b-183) (Synthesis method NF) According to the procedure described in the synthesis method of the compound of Example N-a-143 provided that the reaction was carried out for 18 hours, the compound of Example N-b-1 (22.7 mg), pyridine (23. 8 u 1) and acetyl chloride (40, u 1) were reacted and treated to obtain the title compound (Compound No. N-b-183,16. 3 mg).
[Example N-b-197] Synthesis of 3- [4- (N-benzoyl-N-methylamino)-3- (naphthalen-2-yl) phenyl] propionic acid (Compound No. N-b-197) (Synthesis method NF) According to the procedure described in the synthesis method of the compound of Example N-a-143 provided that the reaction was carried out for 14 hours, the compound of Example N-b-1 (21.8 mg), pyridine (23. 8 g 1) and benzoyl chloride (345 u 1) were reacted and treated. A solution of the obtained residue in methanol (3 ml) was added with 2 N aqueous sodium hydroxide (100, u 1), and stirred at 60°C for 2 hours. The reaction mixture was concentrated under reduced pressure, then made acidic with 5% aqueous hydrochloric acid under ice cooling, and extracted with dichloromethane (5 ml). The organic layer was washed successively with saturated brine, and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Compound No. N-b-197,13. 5 mg).
[Examples N-b-1 to N-b-212] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-B-1 to Table-N-B-5. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of "Syn"with symbols, the starting compounds 1 are mentioned in the columns of "SM1", and the starting compounds 2 are mentioned in the columns of"SM2". dz zx Ru Table-N-B-1 AR Exp. Syn SM1 SM2 Rz Ry Y Zx AR method Mass N-b-1 ND1 N-a-25 H Me H 2-Nap C N-b-2 NA N-b-1 H H H 2-Nap C 306 N-b-3 ND1 H Me H 5-Ind C 309 (M++1) N-b-4 NA N-b-3 H H H 5-Ind C 295 (M++1) N-b-5 ND1 N-a-31 H Me H 1Me-5-Ind N-b-6 NA N-b-5 H H 1 Me-5-Ind N-b-7 ND1 N-a-69 H _-1Hldz 310 (M++1) N-b-8 NA N-b-7 H H 5-1HMz +1) N-b-9 ND1 H Me H 1 N-b-10 NA N-b-9 H H H 1 N-b-11 NC2 N-b-1 CH01 Me Me Me H 2-Nap C 334 (M"+1) N-b-12 NA N-b-11 Me H-H 2-Nap C N-b-13 NC2 N-b-l CH02 Me Et Me H 2-Nap C 348 (M++1) N-b-14 NA N-b-13 Et H H 2-Nap C N-b-15 NC2 N-b-3 CH01 Me Me Me H 5-Ind C N-b-16 NA N-b-15 Me H H 5-Ind C N-b-17 N-b-5 CH01 Me Me H H 1 N-b-18 NA N-b-17 Me H H 1 N-b-19 N-b-9 CH01 Me Me Me H 1 N-b-20 NA N-b-19 Me H H 1 324 (M++1) N-b-21 NB1 Int. Et H Me H 2-Nap C N-b-22 NA N-b-21 H H 2-Nap C N-b-23 NB1 Int. n-12 BRA2 Et H Me H 5-Ind C N-b-24 NA N-b-23 H H H 5-Ind C N-b-25 NB1 BRA3 Et H Me H 1 N-b-26 NA N-b-25 H H H 1 N-b-27 NB1 Int. n-12 BRA4 Et H Me H 1 N-b-28 NA N-b-27 H H H 1Et-5-Ind N-b-29 NB1 Int. n-12 Et H Me H 5-1 N-b-30 NA N-b-29 H H H 5-1 Hldz N-b-31 NB1 Int. n-l Et H Me H 1 C 338 (M++1) N-b-32 NA N-b-31 H H H 1 N-b-33 NB1 Int. n-12 Me H 1 N-b-34 NA N-b-33 H H H 1 N-b-35 NB1 Int. n-12 Et H Me H 2Me-5-Idz C N-b-36 NA N-b-35 H H H 2Me-5-Idz N-b-37 NB1 Int. n-12 BRA9 Et H Me H 5-Bzt C N-b-38 NA N-b-37 H H H 5-Bzt C N-b-39 NB1 Int. n-12 Et H Me H 3-Qu C N-b-40 NA N-b-39 H H 3-Qu C N-b-41 NB1 Int. n-12 Et H Me H 6-Qu C N-b-42 NA N-b-41 H H H 6-Qu C N-b-43 NC2 N-b-21 CH02 Et Et Me H 2-Nap C N-b-44 NA N-b-43 Et H H 2-Nap C exTable-N-B-2 Exp. Syn. SM1 SM2 Rz Ry Y method RTime Mass N-b-45 NC2 N-b-25 CH02 Et Et N-b-46 NA N-b-45 Et H H 1 N-b-47 NB1 Int. n-13 H Me H 5-Ind C N-b-48 NA N-b-47 H H H 5-Ind C N-b-49 NB1 Int. n-13 H Me H 1 N-b-50 NA N-b-49 H H H N-b-51 NB1 Intn-13 H Me H 5-1 N-b-52 NA N-b-51 H H H 5-1 N-b-53 NB1 Int. n-13 nPr H Me H 1 N-b-54 NA N-b-53 nPr H H H 1 N-b-55 NC2 N-b-47 CH01 nPr Me H 5-Ind C (M++J) N-b-56 NA N-b-55 nPr Me H H 5-Ind C N-b-57 NC2 N-b-49 CH01 nPr Me Me H 1 N-b-58 NA N-b-57 nPr Me H H 1 N-b-59 NC2 N-b-51 CHO1 nPr Me Me N-b-60 NA N-b-59 nPr Me H H 5-1 Hldz N-b-61 NC2 N-b-53 CH01 nPr Me Me H 1 N-b-62 NA N-b-61 Me H H 1 N-b-63 NB1 Int. n-14 H Me H 5-Ind C N-b-64 NA N-b-63 H H H 5-Ind C N-b-65 NB1 Int. n-14 H 1 N-b-66 NA N-b-65 H H H 0 N-b-67 NB1 Int. n-14 BRA5 iPr H Me H 5-1 N-b-68 NA N-b-67 H H H 5-1 N-b-69 NB1 Int. n-14 BRA6 iPr H Me H 1 N-b-70 NA N-b-69 H H H 1 N-b-71 NC2 N-b-63 CH01 iPr Me Me H 5-Ind C N-b-72 NA N-b-71 Me H H 5-Ind C N-b-73 NC2 N-b-65 CHO1 iPr Me Me H 1 N-b-74 NA N-b-73 Me H H 1 N-b-75 NC1 N-b-67 CH01 iPr Me Me H 5-1 N-b-76 NA N-b-75 Me H H N-b-77 NC1 N-b-69 Me Me H 1 N-b-78 NA N-b-77 Me H H 1 N-b-79 NB1 Int. n-7 BRA1 nBu H Me H 2-Nap C N-b-80 NA N-b-79 H H H 2-Nap C N-b-81 NB1 Int. n-8 BRA2 nBu H Me H 5-Ind C N-b-82 NA N-b-81 H H H 0 N-b-83 NB Int. n-10 nBu H Me H 5-1 N-b-84 NA N-b-83 H H H 5-1 N-b-85 NB1 Int. n-11 BRA6 nBu H Me H 1 N-b-86 NA N-b-85 H H H 1 N-b-87 NC1 N-b-79 CH01 nBu Me Me H 2-Nap C N-b-88 NA Me H H 2-Nap C N-b-89 NC1 N-b-81 Me H 5-lnd N-b-90 NA N-b-89nBu +D ZX ARTable-N-B-3 Exp. Syn SM1 SM2 Rz Ry Y Zx AU method N-b-91 NC1 N-b-83 CHO N-b-92 NA N-b-91 Me H H 5-1 N-b-93 NC1 N-b-85 CH01 nBu Me Me H N-b-94 NA N-b-93 Me H H 1 N-b-95 NC2 N-b-81 CH02 nBu Et Me H 5-Ind C , el N-b-96 NA N-b-95 Et H H 5-Ind C N-b-97 NC2 N-b-85 CH02 nBu Et Me H 1 N-b-98 NA N-b-97 Et H H N-b-99 NC2 Int. n-9 CH07 Bu H Me H 1 N-b-100 NA N-b-99 H H H 1 N-b-101 NC2 Int. n-10 H Me H 5-1 N-b-102 NA N-b-101iBu H H H 5-lHIdz N-b-103 Int. n-11 H Me H 1 N-b-104 NA N-b-103iBu H H H. N-b-105 H Me H 6-Qu C N-b-106 NA N-b-105iBu H H H 6-Qu G N-b-107 NCI N-b-99 CHO1 iBu Me Me H 1 N-b-108 NA N-b-107iBu Me H H 1 N-b-109 NC1 N-b-103 Me Me H 1Me-5-1Hldz N-b-110 NA N-b-109iBu Me H N-b-111 N-b-105 CH01 iBu Me Me H 6-Qu N-b-112 NA N-b-111 Me H H 6-Qu C N-b-113 N-b-99 CH02 iBu Et Me H 1 N-b-114 NA N-b-113iBu Et H H 1 N-b-115 NC2 N-b-101 CH02 iBu Et Me H 5-1 N-b-116 NA N-b-115 Et H H 5-1 N-b-117 NC2 N-b-103 CHO2 iBu Et N-b-118 Et H H N-b-119 Int. n-16 BRA1 cPen H Me H 2-Nap C N-b-120 NA N-b-119 H H H 2-Nap C N-b-121 Int. n-16 BRA2 cPen H N-b-122 NA N-b-121 H H H 5-Ind C N-b-123 NB1 Int. n-9 BRA3 cPen H Me H 1Me-5-Ind N-b-124 NA N-b-123 H H H 1Me-5-Ind N-b-125 NB1 Int. n-16 BRA5 cPen H Me H 5-lHldz N-b-126 NA N-b-125cPen H H 5-1 N-b-127 NB1 BRA6 cPen H Me N-b-128 NA N-b-127 H H H N-b-129 NB1 Int. n-16 H Me 6-Qu C N-b-130 NA N-b-129 H H H 6-Qu C N-b-131 NB1 Int. n-16 H Me H 5-Bzt C N-b-132 NA N-b-131 H H H 5-Bzt C N-b-133 NC1 N-b-121 CH01 Me Me N-b-134 NA N-b-133 H H 5-Ind C N-b-135 NC1 N-b-123 H 1 N-b-136 NA N-b-135 LEMSTable-N-B-4 LCMS Exp. Syn. SM1 SM2 Rz Ry Y method RTime Mass N-b-137 N-b-'138 N-bis NC2 N-b-123 CH02 cPen Et Me H 1 N-bic NA N-b-1 Et H H 1 N-b-I Et Me H 5-Bzt N-b-142 NA N-b-1 Et H H 5-Bzt C N-b-143 H Me H 2-Nap C388 N-b-144 NA N-b-143 H H 2-Nap C N-b-145 BRA2 cHex H Me H 5-Ind N-b-146 NA N-b-145 H H H N-b-147 Int. n-9 BRA3 cHex H Me H 1 N-b-148 NA N-b-147 H H H 1 N-b-149 Int. n-17 BRA5 cHex H Me H 5-1 N-b-150 NA N-b-149 H H 5-1 N-b-151 NB1 Int. n-17 BRA6 chez Me H 1 N-b-152 NA N-b-157 H H H 1 N-b-1 Int. n-17 H Me H 3-Qu C N-b-154 NA N-b-153 H H H 3-Qu c N-b-155 NC1 N-b-143 CH01 cHex Me Me H 2-Nap C N-b-156 NA N-b-155 Me H H 2-Nap C N-b-157 NC1 N-b-147 CH01 Me Me H 1 N-b-158 NA N-b-157 Me H N N-b-159 NC1 N-b-149 CH01 cHex Me Me H 5-1 N-b-160 NA N-b-'159 Me H H 5-1 N-b-161 NC1 N-b-151 CHO'i Me H 1 N-b-162 NA N-b-161 Me H H 1 N-b-163 NC2 N-b-143 CH02 cHex Et Me H 2-Nap 0 N-b-164 NA N-b-163 Et H H 2-Nap C N-b-165 NC2 N-b-153 Et Me H 3-Qu G N-b-166 NA N-b-165 Et H H 3-Qu C N-b-167 NB1 Int. n-18 BRA2 2 (Me) cHex H Me H 5-Ind C N-b-168 NA N-b-167 (Me) cHex H H H 5-Ind C -b-169NB1 (Me) cHex Me H 1Me-5-Ind N-b-170 NA N-b-169 (Me) cHex H H H 1 N-b-171 NB1 Int. n-18 BRA5 2 (Me) cHex H Me H 5-' N-b-172 NA N-b-1 (Me) cHex H H H N-b-173 NB1 Int. n-18 BRA6 2 (Me) cHex H Me H 1Me-5-lHIdz N-b-174 NA IN-b-1. (Me) cHex N-b-175 n-8 CH025 2-Indane H Me H 5-Ind C N-b-176 NA N-b-175 H H H 5-Ind C N-b-177 NC2 Int. n-9 CH025 2-Indane H Me H'I N-b-178 NA N-b-177 H H 1 N-b-179 NC2 Int. n-10 CH025 2-Indane H Me H N-b-180 NA N-b-179 H H H 5-1 N-b-181 NC2 Int. n-11 CH025 2-Indane H Me H 1 N-b-182 NA N-b-181 H H H 1 +1 Zx ARTable-N-B-5 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method N-b-183 NF N-b-1 AcCI Me 364 (M++1 N-b-184 NA N-base Ac H H 2-Nap C N-b-185 NF N-b-5 Acol Me Ac Me H 1 N-b-186 NA N-b-185 H H 1 N-b-187 NF N-b-11 Me Ac Me H 1 N-b-188 NA N-b-187 H H N-b-189 NF Int. n-11 Ac Ac Me H 1 N-b-190 NA N-b-189 Ac H H 1 N-b-191 NF Int. n-18 Me MeOC (O) Me H 2-Nap C N-b-192 NA N-b-167 H H 2-Nap C N-b-193 NF Int. 8 Me MeOC (o) Me H 1Me-5-Ind CL383 N-b-194 NA N-b-169 H H 1 N-b-195 NF Int. n-18 Me MeOC (o) Me H 1 N-b-196 H H N-b-197 Me Bz H H 2-Nap C 396 (M++1) N-b-198 Me Bz H H 5-lnd 399 (M++1) N-b-199 Me Bz H H 1 N-b-200 NÃ Bz H H 5-1 N-b-201 NA Me Bz H H 1 N-b-202 Me C°0'H H 2-Nap C 412 (M++1) N-b-203 Me Co H 1Me-5-Ind 415 (M++1) nua N-b-204NNFA-N-b-l Me 8 NA H H 2-Nap C 402 (M++I) N-b-20 Me -H 405 (M++1) N-b-206 "n H 2-Nap C 403 (M++1) H N-b-20, H H 1 N-b-208 NÃ Me PhNHC (O) H H 2-Nap C 411 (M++1) N-b-20 Me PhNHC (O) H H 414 (M++1) NA N-b-210 Me cHexNHC (O H H 2-Nap C 417 N-b-211 Me cHexNHC (o H H 1 Me-5-Ind C 420 (M++1) NA I I N-b-212 H H 2-Nap C 430 (M++1) RTime [Example N-c-51] Synthesis of ethyl 3- [4- (imidazol-1-yl)-3-(naphthalen-2-yl)phenyl]acrylate (Compound No. N-c-51) (Synthesis method NB1) According to the procedure described in the synthesis method of the compound of Example N-a-1 (Synthesis method N131) provided that the reaction was carried out for 16 hours, and the column chromatography was performed with chloroform : methanol =100: 1, Intermediate n-33 (300.4 mg), 2-naphthaleneboronic acid (208.3 mg), 2 M aqueous sodium carbonate (900, u 1) and (Ph3P) 4Pd (108.3 mg) were reacted and treated to obtain the title compound (Intermediate N-c-51,304. 2 mg).
[Example N-c-52] Synthesis of 3- [4-(imidazol-l-yl)-3- (naphthalen-2-yl) phenyl] acrylic acid (Compound No. N-c-51) (Synthesis method NA) According to the procedure described in the synthesis method of the compound of Example N-a-2 (Synthesis method NA) provided that the reaction was carried out for 2 hours, the compound of Example N-c-51 (301.2 mg) and 2 N aqueous sodium hydroxide (980 g 1) were reacted and treated to obtain the title compound (Compound No. N-c-52,286. 4 mg).
[Examples N-c-1 to N-c-64] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-C-1 to Table-N-C-3. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of "Syn"with symbols, the starting compounds 1 are mentioned in the columns of "SM1", and the starting compounds 2 are mentioned in the columns of"SM2". zx i Ry O Table-N-C-1 AU Exp. Syn SM1 SM2 NRzRy Y Zx method RTime Mass N-c-1 NB1 Int. n-36 BRAS Me H 2-Nap C 358 (M++1) N-c-2 NA N-c-1 CN H H 2-Nap C 344 (M++1) N-c-3 NB1 Int. n-36 BRA2 [N Me H 5-lnd 347 (M++1) N-c-4 NA N-c-3 CN H H 5-Ind 333 (M++1) N-c-5 NB1 Int. n-36 BRA3 N Me H 1Me-5-Ind 361 (M++1) N-c-6 NA N-c-5 CN H H 347 (M++1) N-c-7 NB1 Int. n-36 BRA5 CN Me H 5-1 348 (M++1) N-c-8 NA N-c-7 CN H H 5-1 334 (M++1) N-c-9 NB1 Int. n-36 BRA6 CN Me H 1 N-c-10 NA N-c-9 CN H H 1 348 (M++1) N-c-11 NB1 Int. n-36 BRA9 N Me H 5-Bzt C 365 (M++1) N-c-12 NA N-c-l H H 5-Bzt C 351 (M++1) N-c-13 Int. n-36 BRA10 CN Me H 3-Qu C 359 (M++1) N-c-14 NA N-c-l H H 3-Qu C 345 (M++1) N-c-15 NB1 Int. n-36 BRA11 Me H 6-Qu C 359 (MN'"+1) N-c-16 NA N-c-15 H H 6-Qu C 345 (N1++1) N-c-17 NB1 Int. n-37 BRA1 Me H 2-Nap C 374 (M++1) N-c-18 NA N-c-17 H H 2-Nap C 360 (M++1) N-c-19 Int. n-37 BRA2 C Me H 5-Ind C 363 (M++1) N-c-20 NA N-c-l H H 5-Ind C 349 (M++1) N-c-21 NB1 Int. n-37 BRA3 0\. N Me H 377 (M++1) N-c-22 NA N-c-21 Ow, H 1 363 (M++1) O-YTable-N-C-2 Exp. Syn. SM2 NRzRy method RTime Mass n N-c-23 NB Me H 5-1 N-c-24 NA N-c-23 (N H 5-1 350 (M++1) n N-c-25 NB1 Intn-37 BRA6 0,, N Me H 1 - N-c-26 NA N-c-25 N 364 (M++1) N-c-27 NB1 Int. n-26 BRA1 CN Me H 2-Nap C 372 (M++1) N-c-28 NA N-c-27 CN H H 2-Nap C 358 (M++1) N-c-29 NB1 Int. n-26 BRA2 CN Me H 5-Ind 361 (M++1) N-c-30 NA N-c-29 CN H 5-Ind 347 (M++1) N-c-31 NB1 Int. n-26 BRA3 CN Me H 1 375 (M++1) N-c-32 NA N-c-31 CN 361 (M++1) N-c-33 NB1 Int. n-26 BRAS CN Me H 5-1 362 (M++1) N-c-34 NA N-c-33 CN H H 5-1 348 (M++1) N-c-35 NB1 Int. n-26 BRA6 CN Me H 1 Me-5-1 ! +1) N-c-36 NA N-c-35 CN H H 1Me-5-1Hldz N-c-37 NB1 Int. n-28 BRAWN Me H 2-Nap C 386 1) N-c-38 NA N-c-37 N-c-39 NB Me H 1 N-c-40 NA N-c-39 375 (M++1) N-c-41 NB1 Int. n-28 BRAWN Me H 5-1 376 (M++1) N-c-42 NA N-c-41 362 (M++1) N-c-43 NB1 Int. n-28 BRAWN Me H 1 390 (M++1) N-c-44 NA N-c-43 376 (M++1) SM1Table-N-C-3 Exp. Y Zx AR method Mass N-c-45 NB1 Int. n-30 BRAS Me H 1Me-5-Ind C 389 N-c-46 NA N-c-45 9 H H 1Me-5- - -375 (M+1) N-c-47 NB1 Me H 5-1HIdz N-c-48 NA N-c-47 CN H H 5-1 N-c-49 NB1 BRA6 ( Me H 1Me-5-1HIdz N-c-50 NA N-c-49 C H H 1 N-c-51 NB1 Int. n-33 BRA1 Et H 2-Nap C 369 N-c-52 j H H 2-Nap C N-c-53 NB1 Int. n-33 BRA3 Et H 1Me-5-Ind N-c-54 NA N-c-53 H H H 1Me-5-Ind I 1 1 344 (M++I) N-c-55 NB1 Int. n-33 BRA6 Et H 1 373 (M++l) N-c-56 NA N-c-55 N, H 11de-5-1 I"f 345 (M++l) N-c-57 NB1 Int. n-35 BRA1 N Et H 2-Nap C 368 (M +1) N-c-58 NA N-c-57 H H 2-Nap C,., - 340 (M+1) N-c-59 NB1 Int. n-35 BRA3 Et H 1Me-5-Ind w N-c-60 NA N-c-59 CN H H 1 "343 (M+1) N-c-61 NB1 Int. n35 BRA5 CN Et H 5-1 358 N-c-62 NA N-c-61 H H 5-1HIdz 330 (M++1) N-c-63 NB1 n-35 BRA6 N Et H 1 372 (M+1) N-c-64 NA N-c-63 - 344 (M+1) [Example N-d-61] Synthesis of ethyl 3- [4- (imidazol-1-yl)-3- (naphthalen-2-yl) phenyl]propionate (Compound No. N-d-51) (Synthesis method NDl) According to the procedure described in the synthesis method of Intermediate n-7 (Synthesis method ND1) provided that the reaction was carried out for 6 hours, the compound of Example N-c-51 (301.5 mg) and 10% palladium/carbon (67.3 mg) were reacted and treated to obtain the title compound (Compound No. N-d-61, 143.5 mg).
[Example N-d-62] Synthesis of 3- [4- (imidazol-1-yl)-3- (naphthalen-2-yl) phenyl] propionic acid (Compound No. N-d-62) (Synthesis method NA) According to the procedure described in the synthesis method of the compound of Example N-a-2 (Synthesis method NA) provided that the reaction was carried out for 3 hours, the compound of Example N-d-61 (140.3 mg) and 2 N aqueous sodium hydroxide (600, u 1) were reacted and treated to obtain the title compound (Compound No. N-d-62, 100.4 mg).
Examples N-d-1 to N-d-74] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-D-1 to Table-N-D-4. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of "Syn"with symbols, the starting compounds 1 are mentioned in the columns of "SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Zx OY Table-N-D-1 Exp. Syn SM1 SM2 NRzRy Y Zx AR method N-d-1 NB1 Int. n-21 BRA1 CN Me H 2-Nap C 360 (M++1) N-d-2 NA N-d-1 CN H H 2-Nap C 346 (M++1) N-d-3 NB1 Int. n-21 BRA2 CN Me H D 4. 79 349 (M++1) N-d-4 NA N-d-3 CN H H 5-Ind D 3. 54 335 (M+tl) N-d-5 NB1 Int. n-21 B H 1Me-5-Ind D 5. 72 363 (M++1) N-d-6 NA N-d-5 _ H 1 Me-5-Ind D 4. 31 349 (M++1) N-d-7 NB1 Int. n-21 BRA5 CN Me H 5-1HIdz 350 (M++1) N-d-8 NA N-d-7 CN H H 5-1 336 (M++1) N-d-9 NB1 Int. n-21 BRA6 CN Me H 1 364 (M+-s-1) N-d-10 NA N-d-9 CN H H 1 350 (M++1) N-d-11 NB1 Int. n-21 BRA9 CN Me H 5-Bzt C 367 (M+tl) N-d-12 NA N-d-l H H 5-Bzt C 353 (M++1) N-d-13 NB1 Int. n-21 BRA10 CN Me H 3-Qu C 361 (M++1) N-d-14 NA N-d-13 H H 3-Qu C 347 (M++1) N-d-15 NB1 Int. n-21 BRA11 Me H 6-Qu C 361 (M++1) N-d-16 NA N-d-15 H H 6-Qu C 347 (M++1) N-d-17 NB1 Int. Me H 2-Nap C 376 (M'"-t-1) N-d-1 8 NA N-d-1 7 0 c \--/N t N-d-l9 Int. n-24 BRA2 0\_N Me H 5-Ind C N-d-20 NA N-d-19 9 N-d-21 NB1 Int. n-24 BRA3 C. Me H 1Me-5-Ind 379 (M N-d-22 NA N-d H 1 Me-5-Ind C 365 (M++1) ARTable-N-D-2 Exp. Syn SM1 SM2 NRzRy Y Zx AR method N-d-23 NB1 Int. n-24 BRA5 O Me H 5-1 Hldz C 366 (M++1) S N-d-24 NA N-d-23 Ou, H H 5-1 ! 352 (M++1) N-d-25 NB1 Int. n-24 BRA6 O, N-d-26 NA N-d-25 0\_, N 366 (M++1) I N-d-27 NB1 Int. BRA9 Ou, Me H 5-Bzt C 383 (M++1) n N-d-28 NA N-d-27 Q, H H 369 (M++1) N-d-29 NB1 Int. n-24 BRA11 H 6-Qu C 377 (M++1) N-d-30 NA N-d-29 N N-d-31 NB1 Int. n-27 BRA1 Me H 2-Nap C 374 (M++1) N-d-32 NA N-d-31 H H 2-Nap N-d-33 Int. n-27 BRA2 CN Me H 5-Ind C 363 (M++1) N-d-34 NA N-d-33 H H 5-Ind C 349 (Mi+1) N-d-35 NB1 Intn-27 BRA3 Me H 1Me-5-Ind 377 (M++1) N-d-36 NA N-d-35 H 1 Me-5-Ind C 363 (M++1) N-d-37 NB1 Int. n-27 BRA5 Me H 5-1 364 (M++1) N-d-38 NA N-d-37 CN 350 (M'"+1) N-d-39 NB1 Int. n-27 BRA6 378 (M++1) N-d-40 NA N-d-39 H 1 Me-5-1 Hldz 364 (M++1) N-d-41 NB1 Int. n-27 BRA11 Me H 6-Qu C 375 (M++1) N-d-42 NA N-d-41 H H 6-Qu C 361 (M++1) N-d-43 NB1 Int. n-27 BRA9 Me H 5-Bzt C 381 (M++1) N-d-44 NA N-d-43 H H 5-Bzt C 367 (M++1) LCMSTable-N-D-3 Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-d-45 NB1 Int. n-29 BRAS--CON Me H 2-Nap C 388 (M++1) - N-d-46 NA N-d-45 H H 2-Nap C 374 (M++1) N-d-47 NB1 Int. n-29 BRA3 Me H 1 N-d-48 NA N-d-47 377 (M++1) N-d-49 NB1 Int. n-29 BRAWN Me H 5-1 +1) N-d-50 NA N-d-49 364 (M++1) N-d-51 NB1 Int. n-29 BRA6 (N +1) N-d-52 NA N-d-51--N 378 (M++1) - N-d-53 NB1 Int. n-29 BRAZEN Me H 3-Qu C 389 (M++1) N-d-54 NA N-d-53 N-d-55 NB1 Int. n-31 BRA3 0r Me H 1Me-5-Ind 391 (M++1) N-d-56 NA N-d-55 CN H H 1 Me-5-Ind 377 (M++1) N-d-57 NB1 Int. n-31 BRA5 CN Me H 5-lIdz 378 (M++1) N-d-58 NA N-d-57 CN H H 5-1 364 (M++1) N-d-59 NB1 Int. n-31 BRA6 Me H 1 392 (M++1) N-d-60 NA N-d-59 Gs H 1 Me-5-1 Hldz N-d-61 ND1 N-c-51 Et H 2-Nap C 371 (M++1) N-d-62 NA N-d-61 H H 2-Nap C 343 (M++1) N-d-63 ND1 N-c-53 N 374 (M++1) N-d-64 NA N-d-63 CN H H 346 (M++1) N-d-65 ND1 N-c-55 H 1 375 (M++1) N-d-66 NA N-d-65 _ C 347 (M++1) LCMSTable-N-D-4 Exp. Syn. SM1 SM2 NRzRy Y Zx AR method Mass N-d-67 ND1 N-c-57 Et H 2-Nap C 370 (M++1) N-d-68 NA N-d-45 H H 2-Nap C 342 (M++1) N-d-69 ND1 N-c-59 N Et H 1 373 (M++1) N-d-70 NA N-d-47 CN H H 1 345 (M++1) N-d-71 N-c-61 CN Et H 5-1 360 (M++1) N-d-72 NA N-d-49 H H 5-1 332 (M++1) N-d-73 ND1 Et H 1 374 (M++1) N-d-74 NA N-d-51 _ H 1 Me-5-1 ! 346 (M++1) [Examples N-e-1 to N-e-204] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table-N-E-1 to Table-N-E-7. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, corresponding methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of"SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Ru\ RYN Table-N-E-1 Exp. Syn SM1 SM2 NRzRy Y AR method RTime Mass N-e-1 NBI Int. n-48 BRA1 Et 2-Nap N-e-2 NA N-e-1 CN H 2-Nap C 375 (M++1) R N-e-3 NB1 Int. n-48 BRA2 CN 378 (M++1) N-e-4 NA N-e-3 H 5-Ind 364 (M++1) v__i N-e-5 NB1 Int. n-48 BRA3 Et 1Me-5-Ind 392 (M++1) N-e-6 NA N-e-5 N-e-7 NB 379 (M++1) N-e-8 NA N-e-7 H 5-1 365 (M++1) \/ N-e-9 NB1 Int. n-48 BRA6 CN 393 (M++1) \/ N-e-10 NA N-e-9 CN H 379 (M++1) N-e-11 NB1 Int. n-48 BRA10 Et 3-Qu N-e-12 NA N-e-11 H 3-Qu C 376 (M++1) N-e-13 Int. n-48 BRA11 6-Qu C 390 (M++1) N-e-14 NA N-e-l 376 (M++1) N-e-15 Int. n-48 BRA12 Et 6-IQ C 390 (M++1) \/ N-e-16 NA N-e-l H 6-IQ C 376 (M++1) \/ N-e-17 NB1 Int. n-49 BRA1 CN Et 2Nap C 375 (M++1) N-e-18 N-e-17 CN H 2Nap C 361 (M++1) N-e-19 NB1 Int. n-49 BRA2 CN Et 5-Ind 364 (M++1) N-e-20 NA N-e-19 CN H 5-Ind C 350 ( ++1) N-e-21 NB1 Int. n-49 BRA3 N Et 1 N-e-22 NA N-e-21 CN H 1Me-5-Ind +1) NTable-N-E-2 _ Exp. Syn SM1 SM2 NRzRy Y AR LCMS method Mass N-e-23 NB1 Int. Et 5-1Hldz N-e-24 NA N-e-23 CN H 5-1 Hldz C 351 (M++1) N-e-25 NB1 Int. n-49 BRA6 379 (M++1) N-e-26 NA N-e-25 9 H 1 365 (M++1) */-\ N-e-27 NB1 Int. n-50 BRA1 Et 2-Nap C 403 (M++1) N-e-28 NA N-e-27--CN H 2-Nap C 389 (M++1) N-e-29 NB1 Int. n-50 N 392 (M++1) rm N-e-30 NA N-e-29-N N-e-31 N81 Int. n-50 BRAN Et 1Me-5-Ind 406 (M++1) N-e-32 NA N-e-31 N 392 (M++1) N-e-33 NB1 Int. n-50 BRA5 Et 5-1 393 (M++1) - N-e-34 NA N-e-33 379 (M++1) N-e-35 NB1 Int. n-50 BRA6-CN Et 1 N-e-36 NA N-e-35--CN 393 (M++1) N-e-37 NB1 Int. n-51 BRA1 2-Nap C 391 (M++1) 0\__/N N-e-38 NA N-e-37 377 (M++1) N-e-39 NB1 Int. BRA3 CCN Et I N-e-40 NA N-e-39 380 (M++1) N-e-41 NB1 Int. n-51 BRA5 ON Et 5-lHldz 381 (M++1) N-e-42 NA N-e-41 O, N-e-43 NB1 Int. n-51 BRA6 O, Et 395 (M++1) N-e-44 NA N-e-43 N g _ LCMSTable-N-E-3 Exp. Syn SM1 SM2 NRzRy N-e-45 NB1 Int. n-52 BRA1 CN Et 2-Nap C 403 (M+1) N-e-46 NA N-e-45 CN H 2-Nap C 389 (M++1) N-e-47 NB1 Int. n-52 BRA3 tfi Et 1Me-5-Ind 406 (M++1) N-e-48 NA N-e-47 CN 392 (M++1) N-e-49 NB Intn-52 BRA5 CN Et 5-1 Hldz C 393 (M++1) N-e-50 NA N-e-49 CN H 5-1 ! 379 (M++1) N-e-51 NB1 Int. n-52 BRA6 CN Et 1 407 (M++1) N-e-52 NA N-e-51----CN H 1 Rz\-Y zon RY Table-N-E-4 Exp. Syn SM1 SM2 Rz Ry Y method Mass N-e-53 NB1 Int. n-53 BRA1 Et Me Et 2-Nap C N-e-54 NA N-e-53 Me H 2-Nap C N-e-55 NB1 Int. n-53 BRA2 Et Me Et 5-lnd N-e-56 NA N-e-55 Me H 5-Ind C N-e-57 NB1 Int. n-53 BRA3 Et Me Et 1 N-e-58 NA N-e-57 Me H 1 N-e-59 NB Int. n-53 BRA5 Et Me Et 5-1 N-e-60 NA N-e-59 H 5-1 N-e-61 NB Int. n-53 BRA6 Et Me Et 1 N-e-62 NA N-e-61 Et Me N-e-63 NB1 Int. n-54 BRA1 Et Et Et 2-Nap C N-e-64 NA N-b-63 Et H 2-Nap C N-e-65 NB1 Int. n-54 BRA2 Et Et Et 5-Ind N-e-66 NA N-b-65 H 5-Ind C N-e-67 NB1 Int. n-54 BRA3 Et Et Et 1 N-e-68 NA N-b-67 Et H 1 N-e-69 NB1 n-54 BRA5 Et Et Et 5-1 N-e-70 NA N-b-69 Et H 5-1 N-e-71 NB1 Int. n-54 BRA6 Et Et Et 1 N-e-72 NA N-b-71 Et H 1 N-e-73 NB1 Int. nPr Me Et 2-Nap C N-e-74 NA N-b-73 H 2-Nap C N-e-75 NB1 Int. n-55 BRA2 nPr Me Et 5-Ind C N-e-76 NA N-b-75 Me H 5-Ind C N-e-77 NB1 Int. n-55 BRA3 nPr Me Et 1Me-5-Ind N-e-78 NA N-b-77 Me H 1Me-5-Ind +1) N-e-79 NB1 Int. n-55 BRA5 nPr Me Et 5-1 N-e-80 NA N-b-79 Me H 5-1 N-e-81 NB1 Int. n-55 BRA6 nPr Me Et 1 N-e-82 NA-b-81 Me H 1 N-e-83 NB1 Int. n-56 BRA1 iPr Me Et 2-Nap C N-e-84 NA N-b-83 Me H 2-Nap C N-e-85 NB1 Int. n-56 BRA2 iPr Me Et 5-Ind C N-e-86 NA N-b-85 Me H 5-Ind C N-e-87 NB1 Int. n-56 BRA3 iPr Me Et 1 N-e-88 NA N-b-87 Me H 1 N-e-89 NB1 Int. n-56 BRA5 iPr Me Et 5-1 N-e-90 NA N-b-89 Me H 5-1 N-e-91 NB1 Int. n-56 BRA6 iPr Me Et 1 N-e-92 NA N-b-91 Me H N-e-93 NB1 Int. n-57 BRA1 nBu Me Et 2-Nap C N-e-94 NA N-b-93 Me H 2-Nap C N-e-95 NB1 Int. n-57 BRA2 nBu Me Et 5-Ind C N-e-96 NA N-b-95 Me H 5-Ind C LOMSTable-N-E-5 Exp. Syn SM1 SM2 Rz Ry Y AR LCMS method RTime Mass N-e-97 NB1 n-57 BRA3 Me Et 1Me-5-Ind N-e-98 NA N-e-97 Me H lMe-5-Ind N-e-99 NB nBu Me Et 5-1 N-e-100 NA N-e-99 Me H 5-l N-e-101 n-57 BRA6 nBu Me Et 1 N-e-102 NA N-e-101 Me H 1 N-e-103 NB1 Int. n-58 BRA1 Bu Me Et 2-Nap C N-e-104 NA N-e-103iBu Me H 2-Nap C N-e-105 Me Et 5-Ind C N-e-106 NA N-e-105 Me H 5-Ind C N-e-107 NB1 Int. n-58 BRA3 iBu Me Et 1 N-e-108 NA N-e-107iBu Me H 1 366 (M++1) N-e-109 NB1 Int. n-58 BRA5 iBu Me Et 5-1 N-e-110 NA N-e-109iBu Me H 5-1 N-e-111 NB1 Int. n-58 BRA6 Bu Me N-e-112 NA N-e-111 Me H 1 N-e-113 n-62 BRA1 Bn H Et 2-Nap C N-e-114 NA N-e-113 H H 2-Nap C N-e-115 n-62 BRA2 Bn H Et 5-Ind C N-e-116 NA N-e-115 H H 5-Ind C N-e-117 n-62 BRA3 Bn H Et 1Me-5-Ind N-e-118 NA N-e-117 H 1 N-e-1 n-62 BRA5 H Et 5-1 N-e-120 NA N-e-119 H H 5-1 N-e-121 n-62 BRA6 Bn H Et 1 N-e-122 NA N-e-121 H 1 Me-5-1 HIdz N-e-123 Int. n-63 4MeBn H Et 2-Nap C N-e-124 NA N-e-1 H 2-Nap C N-e-125 Int. n-63 BRA2 4MeBn Me Et 5-Ind C N-e-126 NA N-e-125 Me H 5-Ind C N-e-127 Int. n-63 BRA5 4MeBn Me Et 5-1 N-e-128 NA N-e-127 Me H 5-1 N-e-129 Int. n-64 BRA2 3MeBn Me Et 5-Ind C N-e-130 NA N-e-129 Me H 5-Ind _ N-e-131 Int. n-64 BRA3 3MeBn Me Et 1Me-5-Ind N-e-132 NA N-e-131 Me H 1 N-e-1 3MeBn Me Et 5-1 N-e-134 NA N-e-133 Me H 5-1 N-e-135 n-65 BRA1 2MeBn Me Et 2-Nap C N-e-136 NA N-e-135 Me H 2-Nap C N-e-137 Int. n-65 BRA3 2MeBn Me Et 1Me-5-Ind N-e-138 NA N-e-137 Me H 1 N-e-139 Int. n-65 BRA6 2MeBn Me Et 1 N-e-140 NA N-e-i H 1 Int.Taele-N-E-6 LOMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-e-1 NB1 Int. n-66 BRA1 4FBn H Et 2-Nap C N-e-142 NA N-e-141 H H 2-Nap C N-e-143 n-66 BRA3 4FBn H Et 1Me-5-Ind +1) N-e-144 NA N-e-143 H 1 N-e-145 NB1 n-66 BRA6 4FBn H Et 1 N-e-146 NA N-e-145 H H 1 N-e-147 n-67 BRA1 3FBn H Et 2-Nap C N-e-148 NA N-e-147 H H 2-Nap C N-e-149 NB1 Int. n-67 BRA2 3FBn H Et 5-Ind N-e-150 NA N-e-149 H H 5-Ind N-e-151 n-67 BRA3 3FBn H Et 1 N-e-152 NA N-e-151 H H 1 N-e-153 NB1 Int. n-68 BRA3 2FBn H Et 1 N-e-154 NA N-e-153 H H 1Me-5-Ind N-e-155 n-68 BRA5 2FBn H Et N-e-156 NA N-e-155 H H 5-1 N-e-157 NB1 Int. n-68 BRA6 2FBn H Et 1 N-e-158 NA N-e-157 H H 1 N-e-159 NB1 Int. n-69 BRA1 4MeOPh H Et 2-Nap C N-e-160 NA N-e-159 H H 2-Nap C N-e-161 NB1 Int. n-69 BRA2 H Et 5-Ind N-e-162 NA N-e-1 H H 5-lnd N-e-1 H Et 7Me-5-Ind N-e-164 H H 1 N-e-165 Int. n-69 BRA5 4MeOPh H Et 5-1 N-e-166 NA N-e-165 H H 5-1 N-e-167 Int. n-70 BRA1 3MeOPh H Et 2-Nap C N-e-168 NA N-e-167 H H 2-Nap C N-e-169 NB1 Int. BRA3 3MeOPh H Et 1 N-e-170 NA N-e-169 H H 1 N-e-171 H Et N-e-172 NA N-e-171 H H lMe-5-lHldz N-e-173 NB1 Int. n-71 BRA5 2MeOPh H Et 5-1 N-e-174 NA N-e-173 H H 5-1 N-e-175 n-71 BRA6 H Et 1 N-e-176 NA N-e-175 H H 1 N-e-177 NB1 Int. n-71 BRA11 H Et 6-Qu C N-e-178 NA N-e-177 H 6-Qu C N-e-179 NB1 Int. n-72 BRA1 4CF3Ph Et 2-Nap C N-e-180 NA N-e-179 H 2-Nap C N-e-181 Int. n-72 BRA3 4CF3Ph H Et 1Me-5-Ind N-e-182 NA N-e-18i +1) N-e-1 Int. n-72 BRA5 4CF3Ph H Et 5-1 Hldz N-e-184 NA N-e-183 H 5-1 N-e-185 n-72 BRA6 H Et N-e-1 H 1 LCMSTable-N-E-7 Exp. Syn Rz Ry Y AR LCMS _ Mass N-e-187 n-73 BRA1 2EtOPh H Et 2-Nap C 441 (M++1) N-e-188 NA N-e-187 H H 2-Nap C 413 (M++1) N-e-189 n-73 BRA3 2EtOPh H Et 1 N-e-190 NA N-e-189 H H 1Me-5- N-e-191 n-73 BRA6 2EtOPh H Et 1 N-e-192 NA N-e-191 H H lMe-5-1 N-e-193 NB1 Int. n-74 BRA1 3iPrOPh H Et 2-Nap C 455 (M++1) N-e-194 NA N-e-193 H H 2-Nap C 427 (M++1) N-e-195 n-74 BRA2 3iPrOPh H Et 5-Ind N-e-196 NA N-e-195 H H 5-lnd N-e-197 Int. n-74 BRA3 3iPrOPh H Et 1 N-e-198 NA N-b-197 H H 1Me-5-Ind N-e-199 3, 5DFPh H Et 1 N-e-200 NA N-b-199 5DFPh H H I N-e-201 Int. n-75 BRA5 3, 5DFPh H Et 5-lHldz N-e-202 NA N-b-201 5DFPh H N-e-203 NB1 Int. BRA6 3, 5DFPh H Et 1 N-e-204 NA N-b-203 5DFPh H H 1 [Example N-f-1] Synthesis of methyl 3- [3- (naphthalen-2-yl)-4- (N-phenylamino) phenyl] propionate (Compound No. N-f-1) (Synthesis method NB2) A solution of Intermediate n-7 (306.1 mg) in dehydrated toluene (1 ml) was added with aniline (1 ml, TCI), palladium acetate (20.2 mg, WAKO), 2- (di-t- butylphosphine) biphenyl (39 mg, Across) and cesium carbonate (863.4 mg, WAKO), and stirred at 90°C for 18 hours. The reaction mixture was added with ethyl acetate (40 ml), and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine.
The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane: ethyl acetate = 4: 1) to obtain the title compound (Compound No. N-f-1, 101.4 mg).
[Examples N-f-1 to N-f-92] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-F-1 and Table-N-F-2. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, corresponding methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of"SM1", and the starting compounds 2 are mentioned in the columns of "SM2". Ou Table-N-F-1 LCMS Exp. Syn SM2 Rz Ry Y Air""''- method RTime Mass N-f-1 Ph H N-f-2 NA N-f-1 H 2-Nap c N-f-3 NB2 Int. BRA14 Ph H Me 5-Ind C N-f-4 NA N-f-3Ph H H 5-Ind C N-f-5 NB2 Int. n-9 Ph H Me 1 N-f-6 NA N-FPh H H 1 N-f-7 Int. n-10 BRA14 Ph H Me 5-1 N-f-8 NA N-FPh H H 5-1 N-f-9 BRA14 Ph H Me 1 N-f10 9 H H 1 N-E-11 Ph Me Me 2-Nap C N-f12 11 Me vu 2-Nap C N-f-13 NB2 N-f-3 Ph Me Me 1 N-f-14 NA N-FPh Me H 1 N-f-15 NB2 N-f-5 Ph Me Me 1 ) N-f-16 NA N-FPh Me H 1 387 (M++1) N-f-I n-7 BORA29 4MePh H Me 2-Nap C N-f-18 NA IN-f-1 H H 2-Nap C N-+-l NB2 Int. n-9 BRA29 4MePh H Me 1 N-f-20 NA N-194MePh H H 1 N-f-21 NB2 Int. n-11 BRA29 4MePh H Me 1Me-5-1HMz N-22 NA N-f-2y H I N-f-23 NB2 Int. n-7 BRA60 3MePh H Me 2-Nap c N-f-24 NA N-F23 H H 2-Nap c N-f-25 NB2 Int. n-9 BRA60 3MePh H Me 1 N-f-26 NA N-F-25 H H 1Me-5-Ind N-f-27 BRA60 3MePh H Me 1 N-f-28 NA N-F-27 H 1 N-f-29 NB2 Int. n-7 BRA59 2MePh H Me 2-Nap c N-f-30 NA N-<-292MePh H H 2-Nap C N-f-31 NB2 Int. n-8 2MePh H Me 5-Ind c N-F-32 NA N-f-31 H H 5-Ind N-f-33 NB2 Int. n-10 BRA59 2MePh H Me 5-1 N-f-34 NA N-f-33 H H N-f-35 NB2 Int. n-7 BORA22 4FPh H Me 2-Nap C N-f-36 NA N-DFPh H H 2-Nap C387 N-f-37 NB2 Int. n-8 BRA22 4FPh H Me 5-Ind C N-f-38 NA N-f-37 H H 5-Ind C N-F-39 NB2 Int. n-9 BRA22 4FPh H Me 1 N-F-40 H H 1 N-f-41 Int. n-7 BRA33 3FPh H Me 2-Nap C401 N-f-42 NA N-DFPh H H 2-Nap c N-f-43 Int. n-10 3FPh H Me N-f-44 NA N-DFPh H H 5-1 N-f-45 Int. n-11 BRA33 3FPh H Me 11 N-f-46 NA N-f-45 AR 0Table-N-F-2 LCMS Exp. Syn SM1 Rz Ry Y AR _ Mass N+47 401 (M++1) N-f-48 NA N-DFPh H H 2-Nap N-49 NB2 Int. BRA32 2FPh H Me N-f-50 NA N-f-49 2FPh H H 5-Ind C N-i-51 NB2 Int. n-t BRA32 2FPh H Me 1 N-f-52 NA N-DFPh H H 1Me-5-1HIdz N-f-53 NB2 Int. n-8 BRA19 4MeOPh H Me 5-Ind C N-f-54 NA N-f-53 H 5-Ind C Nu-55 NB2 Int. BRA19 4MeOPh H Me 5-1 N-f-56 NA N-f-55 H H 5-1 N-f-57 NB2 Int. n-11 4MeOPh Me Me 1Me-5-1HIdz N-f-58 NA N-f-57 Me H 1 N-f-59 NB2 Int. n-9 BRA37 3MeOPh Me N-f-60 NA N-59 Me H 1 N-f-61 NB2 Int. n-10 BRA37 3MeOPh Me Me 5-1HIdz N-f-62 NA N-f-613MeOPh H 5-1 N-f-63 NB2 Int. n-11 H Me N-f-64 NA N-63 H H 1 Nu-65 NB2 Int. n-7 BRA38 2MeOPh H Me 2-Nap C N-f-66 NA N-65 H H 2-Nap C N-f-67 NB2 Int. n-8 BRA38 2MeOPh H Me 5-Ind C N-f-68 NA N-67 H 5-Ind C N-f-69 NB2 Int. BRA38 2MeOPh H Me 1 N-f-70 NA N-f-69 H H Nu-71 NB2 Int. ri-7 BRA41 4CF3Ph H Me 2-Nap C N-f-72 NA N-f-71 H H 2-Nap C N-f-73 NB2 Int. n-9 BRA41 4CF3Ph H Me 1Me-5-Ind N-74 NA N-f-73 H H 1 N-f-75 NB2 Int. n-11 4CF3Ph H Me 1 N-f-76 NA N-75 H H 1 N-f-77 NB2 Int. 4PhOPh H Me 5-Ind C N-f-78 NA N-f-77 H H 5-Ind C N-f-79 NB2 Int. n-9 BRA88 4PhOPh H Me 1 N-f-80 NA N-f-79 H H 1Me-5-Ind N-f-81 NB2 Int. n-10 4PhOPh H Me 5-1 N-f-82 NA N-8 H H 5-1 N-f-83 NB2 Int. n-7 BRA61 2CIPh H Me 2-Nap C N-f-84 NA N-83 H H 2-Nap C N-f-85 NB2 Int. n-9 BRA61 2CIPh N-f-86 NA N-f-85 ! H H N-f-87 NB2 Int. BRA61 2CIPh H Me 5-1 N-f-88 NA N-f-87 H H 5-1 N-f-89 NB2 Int. n-7 BRA73 5DMePh H Me 2-Nap C ) N-f-90 NA N-f89 H H 2-Nap C N-f-91 NB2 Int. n-9 BRA73 H Me'IMe-5-Ind N-f-92 NA H H 1 [Example N-g-33] Synthesis of methyl 3- [4-cyclopentylamino-3-methyl-5- (naphthalen-2- yl) phenyl] propionate (Compound No. N-e-33) (Synthesis method NBl) According to the procedure described in the synthesis method of the compound of Example N-a-1 (Synthesis method NB) provided that the reaction was carried out for 18 hours, and the column chromatography was performed with hexane : ethyl acetate = 4 : 1), the compound of Example N-g-l (91.6 mg), methyl boronate (140.0 mg, Ald), 2 M aqueous sodium carbonate (300 u 1) and (Ph3P) 4Pd (75.5 mg) were reacted and treated to obtain the title compound (Compound-No. N- g-33,41. 3 mg).
Example N-g-251] Synthesis of methyl 3- [4- (N-methyl-N-cyclopentylamino)-3- (N-methylamino)-5- (naphthalen-2-yl) phenyl] propionate (Compound No. N-g-251) (Synthesis method NN1) A solution of Compound No. N-g-131 (102 mg) in DMF (3 ml) was added with 60% sodium hydride (7 mg) under ice cooling, and stirred for 10 minutes.
This reaction mixture was added with methyl iodide (17 u 1), stirred for 10 minutes, then warmed to room temperature, and further stirred for 2 hours. The reaction mixture was poured into water, and added with ethyl acetate (30 ml) for extraction.
The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 3 : 1) to obtain the title compound (Compound No. N-g-251, 30 mg).
[Example N-g-285] Synthesis of methyl 3- [3- (N-dimethylamino)-4- (N-methyl-N-cyclopentylamino)-5- (naphthalen-2-yl) phenyllpropionate (Compound No. N-g-285) (Synthesis method NN2) A solution of Compound No. N-g-131 (102 mg) in DMF (3 ml) was added with 60% sodium hydride (20 mg) under ice cooling, and stirred for 10 minutes.
This reaction mixture was added dropwise with methyl iodide (100, u 1), stirred for 10 minutes, then warmed to room temperature, and further stirred for 16 hours.
The reaction mixture was poured into water, and added with ethyl acetate (30 ml) for extraction. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine, and dried, and then the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (Quad, hexane : ethyl acetate = 3 : 1) to obtain the title compound (Compound No. N-g-285,80 mg).
[Examples N-g-1 to N-g-318] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification including the examples described above are shown in Table-N-G-1 to Table-N-G-7. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of "Syn"with symbols, the starting compounds 1 are mentioned in the columns of "SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Zx yr Ry Tabig-N-G-1 Exp. Syn SM1 SM2 Rz Ry Y Zx AR method Mass N-g-1 NB1 Int. n-39 BRA1 cPen Me Br 2-Nap C N-g-2 NA N-g-1cPen H H Br 2-Nap C N-g-3 NB1 Int. BRA2 cPen Me Br 5-Ind C 441 (All+) N-g-4 NA N-g-3 H H Br 5-Ind (M+) N-g-5 NB1 Int. n-39 BRA3 cPen H Me N-g-6 NA N-g-5 H H Br 1 N-g-7 NB1 Int. n-39 BRA5 cPen H Me Br 5-lHldz N-g-8 NA N-g-7 H H Br 5-1 N-g-9 NB1 Int. n-39 BRA6 cPen H Me Br 1 N-g-10 NA N-g-9 H H Br 1 N-g-11 NB1 Int. n-39 BRA11 H Me Br 6-Qu C N-g-12 NA N-g-11 H H Br 6-Qu C N-g-l Me Me Br 2-Nap C N-g-14 Me H Br 2-Nap C N-g-15 NC2 N-g-5 CH01 cPen Me Me Br 1Me-5-Ind C N-g-16 NA N-g-15 Me H Br 1 Me-5-Ind C N-g-17 Int. n-41 BRA2 nPr H Me Br 5-lnd N-g-18 NA N-g-l H H Br 5-Ind N-g-19 n-41 BRA3 nPr H Me Br 1 Me-5-Ind C N-g-20 NA N-g-19 H H Br 1 Me-5-Ind C N-g-21 NB1 Int. n-41 BRA5 nPr H Me Br 5-1 Hldz C N-g--22 NA N-g-21 H H Br 5-1 Hldz N-g-23 NB1 Int. n-41 BRA11 nPr H Me Br 6-Qu C N-g-24 NA N-g-23 H H Br 6-Qu C N-g-25 NB1 Int. n-43 BRA1 iPr H Me Br N-g-26 NA N-g-25 H H Br 2-Nap C N-g-27 NB1 Int. n-43 BRA2 iPr Me Br 5-Ind C N-g-28 NA N-g-27 H H Br 5-Ind C N-g-29 NB1 Int. n-43 BRA6 iPr H Me Br 1 N-g-30 NA N-g-29 H H Br 1 N-g-31 Int. n-43 BRA10 H Me Br 3-Qu C N-g-32 NA N-g-31 H H Br 3-Qu C N-g-33 NB1 N-g-1 BRA13 cPen H Me Me 2-Nap C N-g-34 NA N-g-33 H H Me 2-Nap C N-g-35 NB1 N-g-3 BRA13 H Me Me 5-Ind C N-g-36 NA N-g-35 H H Me 5-Ind C N-g-37 NB1 N-g-5 BRA13 H Me Me 1Me-5-Ind N-g-38 NA N-g-37 H H Me 1Me-5-Ind N-g-39 N-g-7 BRA13 H Me Me 5-1 N-g-40 NA N-g-39 H H Me 5-1 ! N-g-41 NB1 N-g-9 BRA13 H Me Me 1 N-g-42 NA N-g-41 H Me -1) N-g-43 NC2 N-g-37 CH01 cPen Me Me Me 1 Me-5-Ind C N-g-44 NA N-g-43 Me H Me l Me-5-Ind C 391 \/0Tablg-N-G-2 Exp. Syn SM1 SM2 Rz CMS. method Mass N-g-45 NB1 Int. n-77 BRA1 cPen H Me N02 2-Nap C N-g-46 NA N-g-45 H H N02 2-Nap C N-g-47 Me N02 5-Ind N-g-48 NA N-g-47 H H N02 5-lnd N-g-49 Int. n-77 BRA3 H Me N02 1Me-5-Ind N-g-50 H N02'i N-g-51 n-77 BRA5 cPen H Me N02 5-1 N-52 N-g-52 NA N-g-51 H H N02 5-1 NB1 n-77 BRA6 cPen H Me N02 1 N-g-54 NA N--53 H N02 1 N-g-55 N81 Int. n-78 BRA1 nPr H Me N02 2-Nap C N-g-56 NA N--55 H H N02 2-Nap C N 5 N-57 Int. n-78 BRA2 nPr H Me N02 5-Ind N-g-58 NA N-57 H H N02 5-Ind N NM5 N-g-59 NB nPr H Me N02 1 N-g-60 NA N-g-59 H H N02 1 N-r6 n-78 BRA5 nPr H Me N02 5-1 N-g-62 NA N-g-61 H H N02 5-1 N-gi63 Int. n-78 BRA6 nPr H Me N02 1 N-64 N--64 NA N-g-63 H H N02 1 N-g-65 NB1 Int. H Me N02 2-Nap C N-g-66 NA N-g-65 N02 2-Nap C N-g-67 NB1 iPr H Me N02 5-Ind C382 +D N-g-68 NA H H N02 5-Ind C N46 7 N-g-69 NB1 Int. n-79 BRA3 iPr H Me N02 1 N-g-70 NA N-g-69 iPr H H N02 1 N-g-71 NB1 Int. n-79 BRA5 iPr H Me N02 5-1 N-72 H H N02 5-1 N-g-73 NB1 Int. n-79 BRA6 iPr H Me N02 1 N-g-74 NA N-g-73 iPr H H N02 1 N-75 N81 Int. n-83 BRA1 cPen Me Me N02 2-Nap C N-g-76 NA N-g-75 Me H N02 2-Nap C N-77 n-83 BRA3 Me Me N02 1 N-g-78 NA Me H N02 1 N-g-79 NB Me Me N02 1 N-g-80 NA N-g-79 Me H N02 1 N-g-81 NB1 Int. n-84 BRA1 nPr Me Me N02 2-Nap C N-g-82 NA N-g-81 Me H N02 2-Nap 0 N-g-83 NB Me Me N02 5-Ind C N-g-84 NA N-nPr Me H N02 5-Ind C N-g-85 Int. n-84 BRA3 nPr Me Me N02 1Me-5-Ind N-g-86 NA N-g-85 Me H N02 1 N-87 nPr Me Me N02 5-1 N-r88 NA N-g-87 Me H N02 5-1 Hldz N-g-89 NB1 Int. n-84 BRA6 nPr Me Me N02 1 N-g-90 NA N-g-89 Me H N02 1 N-g-91 NB1 Int. n-85 BRA1 iPr Me Me N02 2-Nap C N-g-92 NA N-91 Me H N02 Ry Y Tablg-N-G-3 Exp. Syn SM1 SM2 Rz Ry Y Zx AR _ N-g-93 N81 Int. n-85 BRA2 iPr Me Me N02 5-Ind N-g-94 NA N-g-93 H N02 5-Ind C382 N-g-95 BRA3 iPr Me Me N02 1Me-5-Ind N-g-96 NA N-g-95 Me H N02 1 N-g-97 NB1 Me Me N02 2 N-g-98 NA N-g-97 Pr N-g-99 NB1 Int. N02 IMe-5-WHz ) N-g-100 NA Me H N02 I N-g-101 ND1 N-g-45 NH2 2-Nap C N-g-102 1 N-g-l Me NH2 5-lnd N-g-104 NA H H NH2 5-Ind C N-g-105 H Me NH2 lMe-5-lnd N-g-106 NA N-105 H H NH2 1 N-g-107 H Me NH2 5-1 Htdz N-g-108 NA N-g-107 H H NH2 5-1 Hldz N-g-109 ND H Me NH2 Me-5-1HHz l) N-110 NA N-g-109 H H NH2 N-g-111 ND1 N-g-55 H Me NH2 2-Nap C N-g-112 NA N-g-l H H NH2 2-Nap C N-g-113 ND1 N-g-57 H Me NH2 5-lnd N-g-114 NA N-g-113 NH2 5-Ind N-115 ND1 N-g-59 H Me NH2 1 N-g-116 NA N-g-l H H NH2 1 N-117 ND1 N-g-61 H Me NH2 5-lHIdz N-g-118 NA N-nPr H H NH2 5-1 Hldz *+1 N-g-l Me NH2 1 N-g-120 NA N-g-l H H NH2 1 N-g-121 ND1 N-g-65iPr H Me NH2 2-Nap C N-g-122 NA N-121 H H NH2 2-Nap C N-g-123. ND1 N-g-67 H Me NH2 5-Ind N-124 NA N-g-123 H H NH2 5-Ind C N-g-125 ND1 N-g-69 H Me NH2 1 N-g-126 NA N-125 H H NH2 1 ++1 N-g-127 ND1 N-g-71 iPr H Me NH2 5-1Hldz N-g-128 NA N-g-127 H H NH2 5-1 HIdz N-g-129 ND1 N-g-73 Me NH2 1 N-g-130 NA N-iPr H H NH2 1 N-g-l Me Me NH2 2-Nap C N-g-132 NA N-g-131 Me H NH2 2-Nap 0 N-g-133 NC1 N-77 Me Me NH2 1 N-g-134 NA N-z133 Me H NH2 I N-135 Me Me NH2 5-1 N-136 NA N-g-135 Me H NH2 5-1 N-g-137 NC1 Me Me NH2 1 N-138 NA N-137 LCMSTablg-N-G-4 Exp. Syn SM1 Y Zx Method RTime Mass N-g-T39 Me Me NH2 2-Nap C N-g-140 NA N-nPr Me H 2-Nap C N--141 Me Me NHZ N-g-142 NA N-g-141 NH2 5-Ind C N-g-143 ND1 N-nPr Me Me NH2 1Me-5-Ind N-g-144 NA N-nPr Me H NH2 1 N-g-145 Me Me NH2 5-lHIdz N-g-146 NA N-nPr Me H NH2 5-lHldz N-g-147 Me Me NH2 1Me-5-1HIdz D N-g-148 H NH2 1 N-g-149 ND1 N-iPr Me Me NH2 2-Nap N-g-150 NA N-iPr Me H NH2 2-Na N-g-151 Me Me NH2 1 N-g-152 Me H NH2 1 N-g-153 I Me Me NH2 5-lHIdz N-g-154 Me H NH2 5-lHIdz N-155 Me NH2 1 N-g-156 NA N-iPr Me H NH2 1 N-g-157 n-80 BRA1 2-Indane H Me N02 2-Nap C N-g-I NA N--157 H H N02 2-Nap n N-g-159 n-80 BRA2 2-Indane H Me N02 5-Ind C N-160 NA N-g-159 H H M02 N-g-161 H Me N02 1Me-5-Ind N-g-162 NA N-g-161 H H N02 1 N-163 Me N02 5-lHIdz N-g-i NA I H H N02 5-1 HIdz N--165 NB1 Int. n-80 BRA6 2-Indane H Me N02 1Me-5-lHIdz N-166 NA N-g-165 H H N02 1 N-167 NB1 Int. n-81 BRA2 cHex H Me N02 5-Ind C N-g-168 H H N02 5-Ind N-169 n-81 BRA3 H Me N02 1Me-5-Ind N-170 NA N-169 H H N02 1Me-5-Ind N--171 Intn-81 BRA5 cHex H Me N02 5-1 N-g-172 NA N--171 H H N02 5-iHIdz N-g-173 NB1 Int. n-81 BRA6 cHex H Me N02 1 N-g-174 NA N-g-173 H N02 1 N--175 2 (Me) cHex H Me N02 2-Na N-g-176 NA N-g-1 (Me) cHex H H N02 2-Na N-g--177 2 (Me) cHex H Me N02 5-Ind N-1-178 NA N-g-177 (Me) cHex H H N02 5-Ind c N-g-179 NB1 Int. n-82 BRA3 2 (Me) cHex H Me N02 1 +1 N-780 (Me) cHex H N02 1Me-5-Ind ) N-g-181 n-82 BRA5 2 (Me) cHex H Me N02 5-1NIdz N-g-182 (Me) cHex H H N02 5-1 N--183 BRA6 2 (Me) H Me N02 1 N--184 NA N-183 H H N02 1 p++ SM2 RTablg-N-G-5 Exp. Syn SM1 SM2 Rz Ry Y Zx AR LCMS method RTime Mass N-g-185 Me Me N02 2-Nap C N--186 NA N-g-185 Me H N02 2-Na P N-187 n-86 BRA3 2-Indane Me Me N02 1Me-5-Ind N-g-188 NA N-g-187 Me H N02 1 N-g-189 NB1 Me Me N02 5-lHIdz N--190 NA N-g-l Me H N02 5-1 N-F191 n-86 BRA6 2-Indane Me Me N02 1Me-5-lNIdz N-g-192 NA N-g-1 Me H N02 1 N-g-193 n-87 BRA1 cHex Me Me N02 2-Nap C N-g-194 NA N-g-193 Me H N02 2-Nap C N-195 n-87 BRA3 cHex Me Me N02 1Me-5-Ind N-g-196 NA N-g-l Me H N02 7 N-YF197 Int. n-87 BRA5 cHex Me Me N02 5-1 N-r198 NA N-g-197 Me H N02 5-1 N-g-l n-87 BRA6 cHex Me Me N02 1Me-5-1HIdz N-g-200 NA N-g-l Me H N02 1 N-g-201 NB1 Int. 4 (Me) cHex Me Me N02 2-Nap C N-g-202 NA N-g-201 (Me) cHex Me H N02 2-Nap C N-g-203 NB1 Int. n-88 BRA3 4 (Me) cHex Me Me N02 1Me-5-Ind N-g-204 NA N-g-2034 (Me) cHex Me H N02 1 N-g-205 NB n-88 BRA6 4 (Me) cHex Me Me N02 N-g-206 (Me) cHex Me H N02 1 N-g-207 ND1 N-g-159 H Me NH2 5-Ind N-g-208 NA N-g-207 H H NH2 5-Ind N-g-209 H Me NH2 1Me-5-Ind N-g-210 NA N-g-209 H H NH2 1 N-g-211 H Me NH2 5-1 N-g-212 NA N-211 H H NH2 5-1 N-g-213 ND1 H Me NH2 1 N-g-214 NA N-213 H H NH2 1 N-g-215 ND1 N-g-167 H Me NH2 5-lnd N-g-216 NA N-g-215 H H NH2 5-lnd N-g-217 ND1 H Me NH2 1Me-5-Ind N-g-218 NA N-g-2 H H NH2 1 N-g-219 ND1 N-g-l H Me NH2 5-1 N-g-220 NA N-219 H H NH2 5-1 N-g-221 ND1 N-g-173 H Me NH2 lMe-5-lHldz N-g-222 NA N-g-221 H H NH2 1Me-5-1Hldz N-g-223 ND1 N-g-l (Me) cHex H Me NH2 5-lnd N-g-224 NA N-g-2234 (Me) cHex H H NH2 5-Ind N-g-225 ND1 N-g-l (Me) cHex H Me NH2 1 N-g-226 NA N-g-225 (Me) cHex H H NH2 1 N-g-227 ND1 N-g-181 (Me) cHex H Me NH2 5-lHldz N-g-228 NA N-g-227 (Me) cHex H H NH2 5-1 N-g-229 ND1 N-g-183 (Me) cHex H Me NH2 1Me-5-1Hldz N-g-230 cHex H H NH2 1 NB1 Intn-86 BRA1 2-IndaneTable-N-G-6 Exp. Syn SM1 SM2 Rz RY-ZX method RTime Mass N-g-231 ND1 N-g-y85 Me Me NH2 2-Nap C _ N-232 Me H NH2 2-Nap C N-g-233 Me Me NH2 IMe-5-Ind 454 (m++J) N-g-234 NA Me H NH2 1 N-g-235 ND1 Me Me NH2 1Me-5-1 N-g-236 NA N-235 Me H NH2 1Me-5-1HIdz N-g-237 ND1 N-g-193 Me Me NH2 2-Nap C N-g-238 NA N-g-237 Me H NH2 2-Nap C N-g-239 ND Me Me NH2 1Me-5-Ind N-g--240 NA N-g-239 Me H NH2 1 N-g-241 ND1 N-r197 Me Me NH2 5-1 N-242 NA N-241 Me H NH2 5-1 N-g-243 ND1 N-199 Me NH2 1Me-5-lHIdz N-g-244 NA N-g-243 H NH2 1Me-5-lHtdz N-g-245 ND1 (Me) cHex Me Me NH2 2-Nap C 431 N-g-246 NA N-g-245 (Me) cHex Me H NH2 2-Nap G N-g-247 ND1 (Me) cHex Me Me NH2 1Me-5-Ind NA NA (Me) cHex Me'H N-g-249 ND1 N-205 (Me) cHex Me Me NH2 1Me-5-1Hldz N-50 N-250 (Me) cHex Me H NH2 1 N-g-251 NN1 N-g-131 CH3I Me Me NHMe 2-Nap C N-g-252 NA N-g-251 Me H NHMe 2-Nap C N-g-253 NN1 N-g-133 Me Me NHMe 1Me-5-Ind N-g-254 NA N-g-253 Me H NHMe 1 N-g-255 NN1 ! Me Me NHMe 1 N-g-256 NA N-g-255 Me H NHMe 1 N-g-257 NN1 N-g-l nPr Me Me NHMe 2-Nap C N-g-258 NA N-257 H NHMe 2-Nap C N-g-259 NN nPr Me Me NHMe 1Me-5-Ind N-g-260 NA N-g-259 Me H N-g-261 NN1 N-r147 nPr Me Me NHMe 1 1++1 N-262 NA N-g-261 Me H NHMe 1 N-g-263 NN1 N-r14ei CH31 Me Me NHMe 2-Nap C N-264 NA N-g-263 Me H NHMe 2-Nap C N-g-265 NN1 N-g-151 Me Me NHMe 1 N-g-266 NA N-g-265 Me H NHMe 1 N-g-267 NN1 N-g-l Me Me NHMe 1 N-g-268 NA N-g-267 Me H NHMe 1 N-g-269 NN1 N-g-231 CH31 Me Me NHMe 2-Nap C 465 N-g-270 NA N--269 Me H NHMe 2-Nap C N-g-271 NN1 N-g-233 CH3I Me Me NHMe lMe-5-lnd N-g-272 NA N-g-271 Me H NHMe 1 N-273 NN1 Me Me NHMe lMe-5-lHldz NA Me H NHMe 1 N-g-275 N-g-237 CH31 Me Me NHMe 2-Nap C N-276 AR LCTablg-N-G-7 Exp. Syn SM1 SM2 Rz Ry Y Zx AR.. method Mass N-g-277 NN1 N-g-239 CH31 Me Me NHMe 1 N-g-278 NA N-g-277 Me H NHMe 1 N-g-279 NN1 N-g-245 CH3I 4Me-cHex Me Me NHMe 2-Nap C445 +1) N-g-280 NA N-g-279 Me H NHMe 2-Nap C N-g-281 NN2 N-g-247 CHAI 4Me-cHex Me Me NMe2 1 +1) N-g-282 NA N-g-281 Me H NMe 1 Me-5-Ind C. N-g-283 NN2 N-g-249 CH31 4Me-cHex Me Me NMe2 1 Me-5-1 N-g-284 NA N-g-283 Me H NMe2 1 N-g-285 NN2 N-g-l Me Me NMe2 2-Nap C N-g-286 NA N-, 2-Nap C N-g-287 NN2 N-g-i Me Me NMe 1 Me-5-Ind N-g-288 NA N-g-287 Me H NMe 1 Me-5-Ind *+1 N-g-289 NN2 N-g-l Me Me NMe 1 Me-5-1 N-g-290 NA N-g-289 Me H NMea 1 N-g-291 NN2 N-g-139 Me Me NMe2 2-Nap C N-g-292 NA N-g-291 H NMe2 2-Nap G N-g-293 nPr Me Me NMe 1 Me-5-Ind N-g-294 NA N-g-293 Me H NMe 1 Me-5-lnd N-g-295 NN2 N-g-147 CHal nPr Me Me NMe2 1 N-g-296 NA N-g-295 Me H NMe2 N-g-297 NN2 N-g-149 CH31 Me Me NMe2 2-Nap C N-g-298 NA N-g-297 Me H NMe2 2-Nap C N-g-299 NN2 N-g-l Me Me NMe2 1 N-g-300 NA N-g-299 Me H NMe2 1 Me-5-Ind N-g-301 NN2 N-g-155 Me Me NMe2 1 N-g-302 NA N-g-301 H NMe2 1 N-g-303 NN2 N-g-231 CH3I 21ndane Me Me NMe2 2-Nap C N-g-304 NA N-g-30321ndane Me H NMe2 2-Nap C N-g-305 NN2 N-g-233 CHal 21ndane Me Me NMe2 1 N-g-306 NA N-g-305 Me H NMe2 1 Me-5-lnd N-g-307 NN2 N-g-235 CHg Me Me NMe 1 Me-5-1 Hldz N-g-308 NA N-g-307 Me H NMe2 1 Me-5-1 Hldz N-g-309 NN2 N-g-237 CH30 Me Me NMea 2-Nap C N-g-310 NA N-g-265 Me H NMea 2-Nap C N-g-311 NN2 N-g-239 CHal Me Me NMe2 N-g-312 NA N-g-267 Me H NMe2 1Me-5-Ind +1) N-g-313 NN2 N-g-245 CH3I 4Me-cHex Me Me NMe2 2-Nap N-g-314 NA N-g-269 Me H NMe2 2-Nap C445 N-g-315 NN2 N-g-247 CH31 4Me-cHex Me Me NMe 1 Me-5-Ind N-g-316 NA N-g-271 H NMe2 1Me-5-Ind N-g-317 NN2 N-g-249 4Me-cHex Me Me NMe2 N--318 NA Me H NMe2 1 Me LCMS[Examples N-h-1 to N-h-458] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table'N'H'l to Table-N-H-10. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, corresponding methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of"SM1", and the starting compounds 2 are mentioned in the columns of"SM2". ex Rz -- Table-N-H-1 Roar R Exp. Syn SM1 SM2 Rz. Ry Y Zx AR method Mass N-h-1 NB1 Int. n-89 BRA1 Bn H Me N02 2-Nap C N-h-2 NA N-FBn H H N02 2-Nap C N-h-3 NB1 Int. n-89 BRA2 Bn H Me N02 5-lnd N-h-4 NA N-h-3 H H N02 5-Ind N-h-5 NB1 Int. n-89 BRA3 Bn H Me N02 1 N-h-6 NA N-h-5 H H N02 1 N-h-7 NB1 Int. n-89 BRA5 Bn H Me N02 5-lHIdz N-h-8 NA N-h-7 H H N02 5-1 Hldz N-h-9 NB1 Int. n-89 BRA6 Bn H Me N02 1 N-h-10 NA N-h-9 H H N02 1 N-h-l1 BRA10 Bn H Me N02 3-Qu C N-h-12 NA N-h-1 H H N02 3-Qu C N-h-13 n-89 BRA11 Bn H Me N02 6-Qu C N-h-14 NA N-h-13 H H N02 6-Qu C N-h-15 Int. n-89 BRA12 Bn H Me N02 6-IQ N-h-16 NA N-h-15 H H N02 6-lQ N-h-17 NB1 Int. n-90 BRA1 4FBn H Me N02 2-Nap C N-h-18 NA N-h-l N02 2-Nap C N-h-19 n-90 BRA2 4FBn H Me N02 5-Ind N-h-20 NA N-h-194FBn H H N02 5-Ind N-h-21 NB1 n-90 BRA3 4FBn H Me N02. 1Me-5-Ind 462 (M++1) N-h-22 NA N-h-21 H H N02 1 N-h-23 NB1 n-90 BRA5 4FBn H Me N02 5-1 N-h-24 NA N-h-23 H H N02 5-1HIdz +D N-h-25 NB1 Int. n-90 BRA6 4FBn H Me N02 1 N-h-26 NA N-h-25 H H N02 1 N-h-27 NB1 Int. n-91 BRA2 2FBn H Me N02 5-Ind N-h-28 NA N-h-27 H H N02 5-Ind C N-h-29 NB1 n-91 BRA3 2FBn H Me N02 1 N-h-30 NA N-h-29 H H N02 1 N-h-31 NB1 Int. n-91 BRA5 2FBn H Me N02 S-1HHz +1) N-h-32 NA N-h-31 H H N02'5-1Hldz N-h-33 NB1 BRA6 2FBn H Me N02 1 N-h-34 NA N-h-33 H H N02 1 N-h-35 NB1 Int. n-92 BRA2 3FBn H Me N02 5-Ind N-h-36 NA N-h-35 H H N02 5-lnd N-h-37 NB1 Int. n-92 BRA3 3FBn H Me N02 1Me-5-Ind N-h-38 NA N-h-37 H H N02 1 N-h-39 NB1 n-92 BRA5 3FBn H Me N02 5-1HIdz N-h-40 NA N-h-39 H N02 5-1 HIdz N-h-41 NB1 n-92 BRA6 3FBn H Me N02 1 N-h-42 NA N-h-41 H H N02 1 N-h-43 NB1 Int. n-93 BRA1 2, 3DFBn H Me N02 2-Nap C N-h-44 NA N-h-43 3DFBn H H N02 2-Nap l N-h-45 NB1 Int. n-93 BRA3 H Me N02 1Me-5-Ind N-h-46 H H N02 1 N 0-YTable-N-H-2 Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-h-47 NB1 n-93 BRA5 2, 3DFBn H Me N02 5-1 N-h-48 NA N-h-47 H H N02 5-1Hldz N-h-49 NB1 Int. n-93 BRA6 2, 3DFBn H Me N02 1 N-h-50 NA N-h-49 3DFBn H H N02 1 467 (M++1) N-h-51 NB1 Int. n-94 BRA2 3, 4DFBn H Me N02 5-Ind N-h-52 NA N-h-513, 4DFBn H H N02 5-lnd 452 (M++l) N-h-53 NB1 Int. n-94 BRA3 3, 4DFBn H Me N02 1Me-5-Ind N-h-54 NA N-h-53 H H N02 1 N-h-55 NB1 n-94 BRA6 4DFBn H Me N02 1 N-h-56 NA N-h-55 4DFBn H H N02 1 N-h-57 NB1 n-95 BRA1 4PhBn Me N02 2-Nap C N-h-58 NA N-h-57 H H N02 2-Nap 503 (m++l) N-h-59 NB1 Int. n-95 BRA2 4PhBn H Me N02 5-lnd C N-h-60 NA N-h-59 H H N02 5-Ind G N-h-61 NB1 Int. n-95 BRA3 4PhBn H Me N02 1 N-h-62 NA N-h-61 4PhBn H H N02 1 N-h-63 N81 Int. n-95 BRA5 4PhBn H Me N02 5-lHldz N-h-64 NA N-h-63 H N02 5-1 Hldz C N-h-65 NB1 Intn-96 2CF3Bn H Me N02 2-Nap N-h-66 NA N-h-65 H H N02 2-Nap G N-h-67 NB1 BRA2 2CF3Bn H Me N02 5-Ind G N-h-68 NA N-h-67 H H N02 5-Ind C N-h-69 NB1 Int. n-96 BRA3 2CF3Bn H Me N02 1Me-5-Ind N-h-70 NA N-h-69 H H N02 1 N-h-71 NB1 Int. n-96 BRA5 2CF3Bn H Me N02 5-1 N-h-72 NA N-h-71 H H N02 5-1 N-h-73 NB1 Intn-97 BRA2 2-TF H Me N02 5-lnd N-h-74 NA N-h-73 H H N02 5-tond C N-h-75 NB1 Intn-97 2-TF H Me N02 1 N-h-76 NA N-h-75 H H N02 1 N-h-77 NB Int. n-97 BRA6 2-TF H Me N02 N-h-78 NA N-h-77 H H N02 N-h-79 NB1 Int. n-98 BRA2 3-TF H Me N02 5-Ind C 436 M''+1 N-h-80 NA N-h-79 H N02 5-Ind N-h-81 NB1 3-TF H Me N02 1 N-h-82 NA N-h-81 H H N02 1 N-h-83 NB1 n-98 BRA5 3-TF H Me N02 5-lHIdz +1 N-h-84 NA N-h-83 H H N02 5-lHIdz N-h-85 NB1 Int. n-98 BRA6 3-TF H Me N02 1Me-5-lHIdz N-h-86 NA N-h-85 H H N02 1 N-h-87 NB1 Int. n-99 BRA1 2-FR H Me N02 2Nap C N-h-88 NA N-h-87 H H N02 2Nap C N-h-89 NB1 Int. BRA2 2-FR H Me N02 5-Ind C N-h-90 H H N02 5-Ind C N-h-91 n-99 BRA6 2-FR H Me N02 1 N-h-92 NA N-h-91 H H N02 1 LCMS, Table-N-H-3 Exp. Syn SM1 SM2 Rz Ry Y AR method Mass N-h-93 NB1 Int. n-100 BRA1 Bn Me N02 2-Nap N-h-94 NA N-h-93 Me H N02 N-h-95 NB1 Int. n-100 BRA2 Bn Me Me N02 5-lnd N-h-96 NA N-h-95 Me H N02 5-Ind C N-h-97 NB1 Int. n-100 BRA3 Bn Me Me N02. lMe-5-Ind N-h-98 NA N-h-97 Me H N02 1 N-h-99 NB1 Int. BRA5 Bn Me Me N02 5-lHIdz N-h-100 NA N-h-99 Me H N02 5-lHIdz N-h-101 NB1 Int. BRA6 Bn Me Me N02 1 1 N-h-102 NA N-h-101 Me H N02 1 N-h-103 NB1 Int. n-100 Bn Me Me N02 3-Qu C N-h-104 NA N-h-1 Me H N02 3-Qu C N-h-105 NB1 Int. Bn Me Me N02 6-Qu 0 N-h-106 NA N-h-1 Me H N02 6-Qu C N-h-107 Bn Me Me N02 6-lQ N-h-108 NA N-h-107 Me H N02 6-lQ N-h-109 NB1 Int. n-101 BRA1 4FBn Me Me N02 2-Nap C N-h-110 NA N-h-109 H N02 2-Nap C N-h-111 NB1 Int. BRA2 4FBn Me Me N02 5-Ind 0 N-h-112 NA N-h-l Me H N02 5-Ind C N-h-113 BRA3 4FBn Me Me N02 1 N-h-114 NA N-h-113 Me H N02 1 N-h-115 Me Me N02 5-lHIdz N-h-116 NA N-h-l Me H N02 5-1 Hldz C N-h-117 NB1 Int. n-101 4FBn Me Me N02 1Me-5-1H 463 (M++15 N-h-118 NA N-h-l H N02 1 N-h-119 NB1 Intn-102 Me Me N02 2-Nap N-h-1 NA N-h-l Me H N02 2-Nap C N-h-121 Int. n-102 BRA3 2FBn Me Me N02 1 N-h-122 NA N-h-1 Me H N02 1 N-h-123 Int. n-102 BRA5 2FBn Me Me N02 5-1 N-h-124 NA N-h-123 Me H N02 5-lHIdz N-h-1 Int. n-1 BRA6 2FBn Me Me N02 1 N-h-126 NA N-h-25 Me H N02 1 5-1 N-h-127 3FBn Me Me N02 2-Nap C N-h-128 NA N-h-1273FBn Me H N02 2-Nap C N-h-129 NB1 Intn-l BRA3 3FBn Me Me N02 1 N-h-130 NA N-h-129 Me H N02 1Me-5-Ind +D N-h-131 BRA5 3FBn Me Me N02 5-1 N-h-132 NA N-h-l Me H N02 5-iHldz N-h-133 Int. n-103 BRA6 3FBn Me Me N02 i N-h-134 NA N-h-l Me H N02 N-h-135 NB1 Int. n-104 2, 3DFBn Me Me N02 2-Nap C N-h-136 NA N-h-l N-h-137 3DFBn Me Me N02 1 466 (RA+-i N N-h-138 NA N-h-137 3DFBn Me H N02 LOMSTable-N-H-4 Exp. SM2 Rz Ry y Zx AR method Mass N-h-l NB1 Int. BRA5 2, 3DFBn Me N-h-140 NA N-h-139 Me H N02 5-1 N-h-141 NB1 Int. n-104 BRA6 2, 3DFBn Me N-h-142 NA N-h-l Me H N02 1 N-h-143 4DFBn Me Me N02 2-Nap C N-h-l NA N-h-143 4DFBn Me H N02 2-Nap C N-h-14 BRA3 3, Me Me N02 1Me-5-lnd N-h-146 NA N-h-145 4DFBn Me H N02 1 N-h-147 Int. n-105 3, 4DFBn Me Me N02 1Me-5-iHIdz N-h-148 NA N-h-1473. Me H N02 1 N-h-149 NB1 Int. n-106 4PhBn Me Me N02 2-Nap C N-h-150 NA N-h-l Me H N02 2-Nap C N-h-1 4PhBn Me Me N02 5-lnd N-h-152 NA N-h-l Me H N02 5-Ind N-h-153 NB1 Int. n-l 4PhBn Me Me N02 1 N-h-154 NA N-h-l Me H N02 1Me-5-Ind N-h-155 Int. n-106 BRA6 4PhBn Me Me N02 1 N-h-156 NA N-h-l H N02 1 N-h-157 Int. n-107 2CF3Bn Me Me N02 2-Nap C N-h-158 NA N-h-l Me H N02 2-Nap C N-h-159 Me Me N02 Slnd N-h-160 NA N-h-l Me H N02 5-Ind N-h-161 Int. n-107 Me N02 1 N-h-162 NA N-h-1 Me H N02 1 N-h-163 BRA5 2CF3Bn Me Me N02 5-1 N-h-164 NA N-h-1 H N02 5-1 N-h-165 Int. n-108 2-TF Me Me N02 2-Nap C N-h-166 NA N-h-165 Me H N02 2-Nap C N-h-167 2-TF Me Me N02 1 N-h-168 NA N-h-1 Me H N02 1 N-h-169 Int. n-108 BRA6 2-TF Me Me N02 1 N-h-170 NA N-h-1 Me H N02 1 N-h-171 3-TF Me Me N02 2-Nap C N-h-l NA N-h-l Me H N02 2-Nap C 436 N-h-1 NB1 Int. n-109 BRA2 3-TF Me Me N02 5-lnd N-h-17'NA Me H N02 5-lnd N-h-175 Int. n-109 3-TF Me Me N02 1Me-5-Ind N-h-176 NA N-h-l Me H N-h-177 NB1 Int. BRA6 3-TF Me Me N02 1Me-5-lHIdz N-h-178 NA N-h-1 H N02 1 N-h-17'NB1 2-FR Me Me N02 2-Nap C. N-h-180 NA N-h-l Me H N02 2-Nap C N-h-18 Int. n-110 BRA2 2-FR Me Me N02 5-lnd N-h-182 NA N-h-181 2-FR Me H N02 5-Ind N-h-183 Int. n-109 Me N02 N-h-184 NA N-h-l Me H N02 1 Syn STable-N-H-5 Exp. Syn SM1 SM2 Rz Ry Zx AU method Mass N-h-18 H Me NH2 2-Nap C N-h-186 NA N-h-185 H H NH2 2-Nap C N-h-187 H Me NH2 5-Ind C N-h-188 NA N-FBn H H NH2 5-Ind C N-h-1 ND1 N-h-5 H Me NH2 1 N-h-190 NA N-h-189 H H NH2 1 N-h-191 ND1 H Me NH2 5-1 N-h-192 NA N-h-191 H H NH2 5-1 HIdz N-h-193 ND1 N-h-9 H Me NH2 1 N-h-194 NA N-h-193 H H NH2 l N-h-195 ND1 N-h-11 H Me NH2 3-Qu C N-h-196 NA N-h-195Bn H H NH2 3-Qu C.. N-h-197 ND1 N-h-13 H Me NH2 6-Qu C N-h-198 NA N-h-197 H H NH2 6-Qu 0 N-h-199 ND1 N-h-174FBn H Me NH2 2-Nap C N-h-200 NA N-h-l H H NH2 2-Nap C N-h-201 ND1 N-h-194FBn H Me NH2 5-Ind G N-h-202 NA N-h-201 H H NH2 5-Ind C N-h-203 ND1 H Me NH2 1Me-5-lnd N-h-204 NA N-h-203 H H NH2 1Me-5-Ind N-h-205 ND1 H Me NH2 5-1 N-h-206 NA N-h-205 H H NH2 5-1 N-h-207 ND1 H Me NH2 1 N-h-208 NA N-h-207 H H NH2 1Me-5-1 N-h-209 ND1 N-h-27 H Me NH2 5-Ind C N-h-210 NA N-h-209 H H NH2 5-Ind C N-h-211 ND1 H Me NH2 1Me-5-Ind N-h-212 NA N-h-211 H H NH2 1 N-h-213 ND1 H Me NH2 5-1 N-h-214 NA N-h-213 H H NH2 5-lHIdz N-h-215 H Me NH2 1 N-h-216 NA N-h H H NH2 1 N-h-217 ND1 N-h-35 H Me NH2 5-Ind N-h-218 NA N-h-217 H H NH2 5-lnd N-h-219 ND1 H Me NH2 N-h-220 NA N-h-219 H H NH2 1 N-h-221 H Me NH2 5-1 r N-h-222 NA N-h-221 H H NH2 5-lHIdz N-h-223 ND1 N-h-41 H Me NH2 1 N-h-224 NA N-h-223 H H NH2 iMe-5-iHIdz N-h-225 ND1 N-h-43 3DFBn H Me NH2 2-Nap C N-h-226 NA N-h-225 3DFBn H H NH2 2-Nap C N-h-227 ND1 N-h-45 H Me NH2 1Me-5-Ind C N-h-228 NA N-h-227 H H NH2 1Me-5-Ind N-h-229 ND1 N-h-47 2, H Me NH2 5-1HHz +1) N-h-230 NA N-h-229 H NH2 5-1 YTable-N-H-6 Exp. Syn SM1 SM2 Rz Ry Y Zx AR Method RTime Mass N-h-231 ND1 N-h-49 3DFBn H NH2 iMe-5-'iHldz N-h-232 NA N-h-231 3DFBn H H NH2 1Me-5-'iHIdz N-h-233 ND1 N-h-51 4DFBn H Me NH2 5-Ind C436 D N-h-234 NA N-h-233 4DFBn H 5-Ind C N-h-235 ND1 4DFBn H I N-h-236 NA 4DFBn H H NH2 1Me-5-Ind N-h-237 ND1 4DFBn H Me NH2 1Me-5-lHIdz N-h-238 NA 4DFBn H H NH2 N-h-239 ND1 N-h-57 H Me NH2 2-Nap C N-h-240 NA N-h-239 H H NH2 2-Na N-h-241 ND1 N-h-59 H Me NH2 5-Ind N-h-242 NA N-h-241 NH2 5-Ind N-h-243 ND1 N-h-614PhBn H Me NH2 N-h-244 NA N-h-243 H H NH2'I N-h-245 ND1 H Me NH2 5-lHIdz N-h-246 NA N-h-245 H H NH2 5-lHIdz N-h-247 ND1 N-h-652CF3Bn H Me NH2 2-Na N-h-248 NA N-h-247 H H NH2 2-Nap N-h-249 ND1 H Me NH2 5-Ind N-h-250 NA N-h-249 H H NH2 5-Ind N-h-251 ND1 H Me NH2 1Me-5-Ind '+1 N-h-252 NA N-h-251 NH2 1 N-h-253 ND1 N-h-71 H Me NH2 5-iHIdz N-h-254 NA N-h-253 H H NH2 5-1 HIdz N-h-255 H Me NH2 N-h-256 NA N-h-255 H H NH2 5-Ind N-h-257 ND1 H Me NH2 1Me-5-Ind N-h-258 NA N-h-257 H H NH2 1 N-h-259 ND1 H Me NH2 1 N-h-260 NA N-h-259 H H NH2 1Me-5-lHIdz N-h-261 ND1 H Me NH2 5-Ind N-h-262 NA H NH2 5-Ind c N-h-263 ND1 H Me NH2 7 N-h-264 NA N-h-263 H H NH2 1 N-h-265 ND1 N-h-83 H Me NH2 5-1 HIdz N-h-266 NA N-h-265 H H NH2 5-1 N-h-267 ND1 N-h-85 H Me NH2 1Me-5-lHIdz N-h-268 NA N-h-267 H H NH2 1 N-h=269 H Me NH2 2Nap C N-h-270 NA N-h-269 H H NH2 2Na N-h-271 H Me NH2 5-Ind C N-h-272 NA N-h-2712-FR H NH2 5-Ind C IN-h-273 N-h-274 NA N-h-273 LCMSTable-N-H-7 Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-h-275 ND1 N-h-93 Me Me NH2 2-Nap C N-h-276 NA N-h-275 Me H NH2 N-h-277 ND1 Me Me NH2 5-Ind N-h-278 NA N-h-277 Me H NH2 5-lnd N-h-279 ND1 Me Me NH2 1 N-h-280 NA N-h-279 Bn Me H NH2 IMe-5-Ind N-h-281 ND1 N-h-99 Me Me NH2 5-1 N-h-282 NA N-h-281 NH2 5-1 Hldz N-h-283 ND1 Me Me NH2 1 N-h-284 NA N-h-283 Me H NH2 1 N-h-285 ND1 N-h-103 Me Me NH2 3-Qu C N-h-286 NA N-h-285 Me H NH2 3-Qu C N-h-287 ND1 N-h-105 Me Me NH2 6-Qu C426 D N-h-288 NA N-h-287 Me H NH2 6-Qu C N-h-289 ND1 N-h-107 Me Me NH2 6-lQ N-h-290 NA N-h-289 Me H NH2 6-10 C N-h-291 ND1 N-h-1094FBn NH2 2-Nap C_ N-h-292 NA N-h-291 NH2 2-Nap N-h-293 ND1 N-h-l Me Me NH2 5-Ind N-h-294 NA N-h-293 Me H NH2 5-Ind C N-h-295 ND1 Me Me NH2 1 N-h-296 NA N-h-295 Me H NH2 1 N-h-297 ND1 N-h-115 Me Me NH2 5-1 N-h-298 NA N-h-297 Me H NH2 5-lHldz N-h-299 ND1 N-h-117 Me Me NH2 1Me-5-lHIdz N-h-300 NA N-h-299 Me H NH2 1 N-h-301 ND1 Me Me NH2 2-Nap C N-h-302 NA N-h-301 Me H NH2. 2-Nap C N-h-303 ND1 N-h-121 Me Me NH2 1 N-h-304 NA N-h-303 Me H NH2 _1 N-h-305 ND1 Me Me NH2 5-1 N-h-306 NA N-h-305 Me H NH2 5-1 N-h-307 ND1 N-h-125 Me NH2 1Me-5-1HHz +1) N-h-308 NA N-h-307 Me H NH2 1Me-5-1HHz -H) N-h-309 ND1 Me Me NH2 2-Nap C N-h-310 NA N-h-309 Me H N-h-311 ND1 Me Me NH2 1Me-5-Ind N-h-312 NA N-h-311 Me H NH2 1 N-h-313 ND1 N-h-131 Me Me NH2 5-1 N-h-314 NA N-h-313 Me H NH2 5-1 Hldz N-h-315 ND1 Me Me NH2 1 N-h-316 NA N-h-315 Me H NH2 1 N-h-317 ND1 N-h-135 Me Me NH2 2-Nap C N-h-318 NA N-h-317 3DFBn Me H NH2 2-Nap C N-h-319 ND1 Me Me NH2 1 N-h-320 NA N-h-319 H NH2 1 LCMSTable-N-H-8 Exp. Syn SM1 SM2 Rz Ry Y Zx AR _. _ Mass N-h-321 ND1 N-h-139 3DFBn Me Me NH2 5-lHldz N-h-322 NA N-h-321 3DFBn Me H NH2 5-lHTdz N-h-323 ND1 N-h-141 Me Me NH2 1 N-h-324 NA N-h-323 3DFBn Me H NH2 lMe-5-1Hldz N-h-325 ND1 N-h-143 4DFBn Me Me NH2 2-Nap N-h-326 NA N-h-325 4DFBn Me H NH2 2-Nap C N-h-327 ND1 4DFBn Me Me NH2 N-h-328 NA N-h-327 4DFBn Me H NH2 1 N-h-329 ND1 N-h-147 4DFBn Me Me NH2 N-h-330 NA N-h-329 4DFBn Me H NH2 1 N-h-331 ND1 N-h-149 Me Me NH2 2-Nap C N-h-332 NA N-h-331 Me H NH2 2-Nap C N-h-333 ND1 N-h-151 Me Me NH2 5-Ind N-h-334 NA N-h-333 Me H NH2 5-Ind N-h-335 ND1 N-h-1 Me Me NH2 1 N-h-336 NA N-h-335 Me H NH2 1 N-h-337 ND1 N-h-155 Me Me NH2 1 N-h-338 NA N-h-337 Me H NH2 1 N-h-339 ND Me Me NH2 2-Nap C N-h-340 NA N-h-339 Me H NH2 2-Nap C N-h-341 ND1 Me Me NH2 5-lnd N-h-342 NA N-h-341 Me H NH2 5-lnd N-h-343 ND1 N-h-1 Me NH2 1 N-h-344 NA N-h-343 NH2 1 N-h-345 ND1 N-h-163 Me NH2 5-1 N-h-346 NA N-h-345 Me H NH2 5-1 N-h-347 ND1 N-h-165 Me Me NH2 2-Nap C N-h-348 NA N-h-347 Me H NH2 2-Nap C N-h-349 ND1 Me Me NH2 1Me-5-Ind +1) N-h-350 NA N-h-349 Me H NH2 1 N-h-351 ND1 N-h-169 Me Me NH2 1 N-h-352 NA N-h-351 Me H NH2 1 N-h-353 ND1 N-h-171 Me Me NH2 2-Nap C N-h-354 NA N-h-353 H NH2 2-Nap 417 (m++i) N-h-355 ND1 N-h-173 Me Me NH2 5-Ind N-h-356 NA N-h-355 Me H NH2 5-lnd N-h-357 ND1 N-h-175 Me Me NH2 1Me-5-Ind N-h-358 NA Me H flH2'1 ++1 N-h-359 ND1 Me Me NH2 lMe-5-lHldz N-h-360 NA N-h-359 H NH2 1 N-h-361 ND1 N-h-1 Me Me NH2 2-Nap C N-h-362 NA N-h-361 Me H NH2 2-Nap C N-h-363 ND1 N-h-181 Me Me NH2 5-Ind N-h-364 NA N-h-363 Me H NH2 5-Ind C N-h-365 ND1 N-h-1832-FR N-h-366 NA N-h-365 H NH2 1Me-5-1HHz LCMSTable-N-H-9 Exp. Syn SM1 SM2 Rz Ry Y Zx AR _, method RTime Mass N-h-367 NN1 N-h-275 CH31 Bn Me Me NHMe 2-Nap C N-h-368 NA N-h-367 Me H NHMe 2-Nap _ N-h-369 NN1 N-h-279 CH3I Bn Me N-h-370 NA Me H NHI@ie 1 N-h-371 NN1 N-h-283 CHsl Me Me NHMe 1 N-h-372 NA N-h-371 Me H NHMe 1 N-h-373 NN1 N-h-285 CH31 Bn Me Me NHMe 3-Qu C N-h-374 NA N-h-373 Me H NHMe 3-Qu C N-h-375 NN1 N-h-289 CH31 Bn Me Me NHMe. 6-IQ N-h-376 NA N-h-375 Me H NHMe 6-lQ N-h-377 NN1 N-h-291 OH, 4FBn Me Me NHMe 2-Nap C N-h-378 NA N-h-377 Me H NHMe 2-Nap C N-h-379 NN1 N-h-295 CH31 4FBn Me Me NHMe 1Me-5-Ind N-h-380 NA N-h-379 Me H NHMe 1 Me-5-Ind 446 (M++l N-h-381 NN1 N-h-299 CH31 4FBn Me Me NHMe 1 N-h-382 NA N-h-381 Me H NHMe 1 N-h-383 NN1 N-h-301 CH31 2FBn Me Me NHMe 2-Nap C457 +D N-h-384 NA N-h-383 Me H NHMe 2-Nap C N-h-385 NN1 N-h-303 CH31 2FBn Me Me NHMe 1 Me-5-Ind 460 (M++l) N-h-386 NA N-h-385 Me H NHMe 1 N-h-387 NN1 N-h-307 CH31 2FBn Me Me NHMe 1 N-h-388 NA N-h-387 Me H NHMe N-h-389 NN1 N-h-309 CH31 3FBn Me Me NHMe 2-Nap C N-h-390 NA N-h-389 Me H NHMe 2-Nap C N-h-391 NN1 N-h-311 CH, 3FBn Me Me NHMe 1Me-5-Ind N-h-392 NA N-h-391 Me H NHMe 1 N-h-393 NN 2, 3DFBn Me Me NHMe 2-Nap C N-h-394 NA N-h-393 3DFBn Me H 2-Nap C N-h-395 NN1 N-h-323 CH3I 3DFBn Me Me NHMe 1 N-h-396 NA N-h-395 3DFBn Me H NHMe 1 N-h-397 NN1 N-h-327 CHg 4DFBn Me Me NHMe 1 N-h-398 NA N-h-397 4DFBn Me H NHMe 1 N-h-399 NN1 N-h-331 CH31 Me Me NHMe 2-Nap C N-h-400 NA N-h-399 Me H NHMe 2-Nap C N-h-401 NN1 N-h-337 31 4PhBn Me Me NHMe 1Me-5-1HIdz +1) N-h-402 NA N-h-401 Me H NHMe I N-h-403 NN1 N-h-339 CH31 2CF3Bn Me Me NHMe 2-Nap C N-h-404 NA N-h-403 Me H NHMe 2-Nap C N-h-405 NN1 N-h-343 CH31 2CF3Bn Me Me NHMe 1 N-h-406 NA N-h-405 Me H NHMe lMe-5-lnd N-h-407 NN1 N-h-347 CH31 2-TF Me Me NHMe 2-Nap C N-h-408 NA N-h-407 Me H NHMe 2-Nap N-h-409 NN1 N-h-357 CH31 3-TF Me Me NHMe 1 N-h-410 NA N-h-409 Me H NHMe 1 N-h-411 NN1 N-h-365 CH31 2-FR Me Me NHMe 1 N-h-412 NA N-h-411 Me H NHMe 1 LCMS-"Table-N-H-10 Exp. Syn SM1 SM2 Rz Ry Y Zx AR. _ Mass N-h-413 NN2 N-h-275 CH31 Bn Me Me NMe2 2-Nap C N-h-414 NA N-h-413 H NMe2 2-Nap C N-h-415 NN2 N-h-279 CH31 Bn Me Me NMe2 1 N-h-416 NA N-h-415 Me H NMe2 1 N-h-417 N-h-283 CH3I Bn Me Me NMe2 1Me-5-lHldz N-h-418 NA N-h-417 Me H NMe2 1Me-5-lHIdz N-h-419 NN2 N-h-285 CH31 Bn Me Me NMe2 3-Qu c N-h-420 NA N-h-419 Me H NMe2 3-Qu C N-h-421 NN2 N-h-289 CH31 Bn Me Me NMe2 6-IQ N-h-422 NA N-h-421 Me H N-h-423 NN2 N-h-291 CH31 4FBn Me Me NMe2 2-Nap C N-h-424 NA N-h-423 Me H NMe2 2-Nap C N-h-425 NN2 N-h-295 CH31 4FBn Me Me NMe2 IMe-5-hd N-h-426 NA N-h-425 Me H NMe2 1 N-h-427 NN2 N-h-299 CHO 4FBn Me Me NMe2 1 N-h-428 NA N-h-427 Me H NMe2 1 N-h-429 NN2 N-h-301 CH31 2FBn Me Me NMe2 2-Nap C N-h-430 NA N-h-429 Me H NMe2 2-Nap C N-h-431 NN2 N-h-303 CH31 2FBn Me Me NMe2'I N-h-432 NA N-h-431 Me H NMe2 1Me-5-Ind N-h-433 NN2 N-h-307 CH31 2FBn Me Me NMe2 1 N-h-434 NA N-h-433 Me H NMe2 N-h-435 NN2 N-h-309 CH31 3FBn Me Me NMe2 2-Nap C N-h-436 NA N-h-435 Me H NMe2 2-Nap C N-h-437 NN2 N-h-311 CHaI 3FBn Me Me NMe2 1 N-h-438 NA N-h-437 Me H NMe2 1 N-h-439 NN2 N-h-317 CH31 3DFBn Me Me NMe2 2-Nap C N-h-440 NA N-h-439 3DFBn Me H NMe2 2-Nap C N-h-441 NN2 N-h-323 Me Me NMe2 1 N-h-442 NA N-h-441 Me H NMe2 1 N-h-443 NN2 N-h-327 XCH310 3, 4DFBn Me Me NMe2 1Me-5-Ind N-h-444 NA N-h-443 4DFBn Me H NMe2 1 N-h-445 NN2 N-h-331 CH31 4PhBn Me Me NMe2 2-Nap C N-h-446 NA N-h-445 Me H NMe2 N-h-447 NN2 N-h-337 CH3I 4PhBn Me Me NMe2 1 N-h-448 NA N-h-447 Me H NMe2 1 N-h-449 NN2 N-h-339 CH31 2CF3Bn Me Me NMe2 2-Nap C N-h-450 NA N-h-449 Me H NMe2 2-Nap C N-h-451 NN2 N-h-343 CH31 Me Me NMe2 1Me-5-Ind N-h-452 NA N-h-451 Me H NMe2 N-h-453 NN2 N-h-347 CH31 2-TF Me Me NMe2 2-Nap C N-h-454 NA N-h-453 Me H NMe2 2-Nap G N-h-455 NN2 N-h-357 CH31 3-TF Me Me NMe2 1 N-h-456 NA Me H NMe2 1Me-5-lnd N-h-457 NN2 N-h-365 CH31 2-FR Me Me NMe2 1 N-h-458 NA N-h-457 Me H NMe2 1 [Examples N-i-1 to N-i-138] Typical examples of the compounds of the present invention that can be obtained by reacting and treating corresponding starting compounds using any of the methods described in the present specification are shown in Table-N-1-1 to Table-N-I-8. In the tables, the compound numbers are mentioned in the columns indicated as"Exp.". In the tables, used methods among the aforementioned synthesis methods are shown in the columns of"Syn"with symbols, the starting compounds 1 are mentioned in the columns of "SM1", and the starting compounds 2 are mentioned in the columns of"SM2". Zx Rz) =\ ny OY N Table-N-1-1 Exp. Syn SM1 SM2 NRzRy Zx method Mass N-i-1 NB1 Int. Me N02 2-Nap C 405 (M++1) N-i-2 NA N-i-1 CN H N02 2-Nap C 391 (M++1) N-i-3 NB1 1 Me N02 5-1Ind N-i-4 NA N-i-3 CN H N02 5-lInd 380 (M++1) N-i-5 NB1 Int. N02 1 Me-5-Ind 408 (M++1) N-i-6 NA N-i-5 H N02 1 394 (M++1) N-i-7 NB 1 Me N02 5-1 ! 395 (M++1) N-i-8 NA N-i-7 CN H N02 5-1 ! 381 (M++1) N-i-9 NB1 Int Me N02 1iMe-5-1Hldz N-i-10 NA N-i-9 H N02 1 395 (milz N-i-11 Me N02 5-Bzt C 412 (M++1) N-i-12 NA N-i-11 H N02 5-Bzt C 398 (M++1) N-i-13 NB1 Int. 10 CN Me N02 3-Qu C 406 (M++1) N-i-14 NA N-i-13 H N02 3-Qu C 392 (M++1) N-i-15 NB1 Int. 11 CN Me N02 6-Qu C 406 (M++1) N-i-16 NA N-i-15 H N02 6-Qu C 392 (M++1) Int. n- N-i-17 NB1 I112 Me N02 2-Nap C 421 (M++1) n N-i-18 NA N-i-17 H N02 2-Nap C 407 (M++1) Int. n- N-i-19 Me N02 5-lInd 410 (M++1) n N-i-20 NA N-i-19 N Int. n- N-i-21 NB1 112 Me N02 1Me-5-Ind 424 (M++1) N-i-22 NA N-i-21 ON H N02 1 Me-5-Ind 410 (M++1) ARTable-N-I-2 Exp. Syn SM1 SM2 NRzRy Y method RTime Mass Int n- N-i-23 NB1 BRA5 N Me N02 5-lHldz 411 (M N-i-24 NA N-i-23 O, 5-1 HIdz C 397 (M++1) N-i-25 NB1 BRA6 Me N02 425 (M++1) 112 N-i-26 NA N-i-25 O,, 411 (M++1) N-i-27 NB1 In1tin3-BRA1 Me N02 2-Nap C 419 1) 113 N-i-28 NA N-i-27 CN H N02 2-Nap C 405 (M N-i-29 NB1 Int. Me N02 5-1 Ind 408 (M++1) 113 N-i-30 NA N-i-29 CN N02 5-1 394 (M++1) N-i-31 NB1 Me N02 1 422 (M++1) 113 N-i-32 NA N-i-31 CN H N02 1 408 (M++1) N-i-33 NB1 Inta-BRA5 Me N02 5-1 ! 409 (M++1) N-i-34 NA N-i-33 CN H N02 5-1 ! 395 (M++1) N-i-35 NB1 I113 6 Me N02 1 tM'+i) N-i-36 NA N-i-35 CN H N N-i-37 NB1 Int. Me N02 6-Qu C 420 (M++1) N-i-38 NA N-i-37 CN H N02 6-Qu C 406 (M++1) N-i-39 NB1 I114 N Me N02 2-Nap C 433 (M++1) 114 N-i-40 NA N-i-39-N N-i-41 NB1 I114 N 437 (M++1) 114 N-i-42 NA N-i-41 423 (M++1) N-i-43 NB N02 5-1 HIdz C 423 (M++1) 114 N-i-44 NA N-i-43 409 (M++1) Zx ARTable-N-I-3 Exp. Exp. Syn SM1 I method N-i-45 ''."BRA6-/N +1) N-i-45 N-i-46 NA N-i-455-CN N-i-47 NB1 Me N02 436 (M++1) N-i-48 NA N-i-47 CN H N02 422 (M++1) N-i-49 NB1 Intn-BRA5 Me N02 5-lHldz N-i-50 NA N-i-49 H N02 5-1 Hldz C 409 (M++1) N-i-51 NB1 'g'BRA6 N Me N02 lMe-5-1Hldz 437 (M++1) N-i-52 NA N-i-51 N02 1 423 (M++1) N-i-53 ND1 N-i-1 NH2 2-Nap C 375 (M 1 N N-i-54 NA N-i-53 CN H NH2 2-Nap C 361 (M++1) N-i-55 ND1 N-i-3 CN Me NH2 5-1 364 (M++1) N-i-56 NA N-i-55 CN H NH2 5-llnd 350 (M++1) N-i-57 ND1 N-i-5 Me NH2 1 N-i-58 NA N-i-57 H NH2 1Me-5-Ind 364 (M++1) N-i-59 ND1 N-i-7 CN Me NH2 5-1 365 (M++1) N-i-60 NA N-i-59 CN H NH2 5-1 Hldz N-i-61 N-i-9 CN Me NH2 1 379 (M++1) N-i-62 NA N-i-61 CN H NH2 1 365 (M++1) N-i-63 ND1 N-i-11 Me NH2 5-Bzt C 382 (M++1) N-i-64 NA N-i-63 [N NH2 5-Bzt C 368 (M++1) N-i-65 ND1 Me NH2 3-Qu C 376 (M++1) N-i-66 NA N-i-65 _ NH2 3-Qu C 362 (M Table-N-I-4 Exp. Syn SM1 SM2 NRzRy Y Zx AR method N-i-67 ND Me NH2 6-Qu C 376 (M++1) N-i-68 NA N-i-67 CN H NH2 6-Qu C 362 (M++1) N-i-69 ND1 N-i-17 NH2 2-Nap 391 (M++1) N-i-70 NA N-i-69 CF'N H NH2 2-Nap C 377 (M++1) N-i-71 ND1 N-i-19 cTN Me NH2 5-1 380 (M++1) N-i-72 NA N-i-71 NH2 5-llnd 366 (M++1) \_, N H N-i-73 ND1 N-i-21 C 394 (M++1) -JN Me NH2 N-i-74 NA N-i-73 0\_, 380 (M++1) u n N-i-75 ND1 N-i-23 O 381 (M++1) n N-i-76 NA N-i-75 O, 367 (M++1) n N-i-77 ND1 N-i-25 ou, Me NH2 1 n N-i-78 NA N-i-77 O, N-i-79 ND1 N-i-27 CN Me NH2 2-Nap C 389 (M++1) N-i-80 NA N-i-79 H NH2 2-Nap C 375 (M++1) N-i-81 ND1 N-i-29 CN Me NH2 5-lInd 378 (M++1) N-i-82 NA N-i-81 CN H NH2 5-lInd 364 (M++1) N-i-83 ND1 NH2 1Me-5-Ind 392 (M++1) N-i-84 NA N-i-83 CN H NH2 1 N-i-85 ND Me NH2 5-1 379 (M++1) N-i-86 NA N-i-85 CN H NH2 5-1 365 (M++1) N-i-87 ND1 N-i-35 Me NH2 1 393 (M++1) N-i-88 NA N-i-87 CN H NH2 1 LCMSTable-N-1-5 Exp. Syn SM1 SM2 NRzRy Y Zx AR method N-i-89 ND1 N-i-37 Me NH2 6-Qu C 390 (M++1) N-i-90 NA N-i-89 H NH2 6-Qu C 376. (M++1) N-i-91 ND1 N-i-39 XN Me NH2 2-Nap C 403 (M++1) N-i-92 NA N-is-N H NH2 2-Nap C 389 (M++1) N-i-93 ND1 N-is-N Me NH2 1 406 (M++1) N-i-94 NA N-inn H NH2 1 392 (M++1) N-i-95 ND1 N-i-43 N-i-96 NA N-is-N H NH2 5-1 Idz C 379 (M++1) N-i-97 ND1 N-is-N Me NH2 1 407 (M++1) N-i-98 NA N-is-N H NH2 1 N-i-99 ND1 N-i-47 CN Me NH2 1Me-5-Ind 406 (M++1) N-i-100 NA N-i-99 CN H NH2 1 392 (M++1) N-i-101 I NH2 5-1 393 (M++1) N-i-102 NA N-i-101 CN H NH2 5-lIdz 379 (M++1) N-i-103 ND1 N-i-51 C Me NH2 1 N-i-104 NA N-i-103 H NH2 1 393 (M++1) N-i-t N-i-53 CH31 ! 2-Nap C 389 N-i-106 NA N-i-10 H NHMe 2-Nap C 375 (M++1) N-i-107 NN1 N-i-57 CH31 Me NHMe 1Me-5-Ind 392 (M++1) N-i-108 NA N-i-107 CN H NHMe 1 378 (M++1) N-i-109 NN1 N-i-61 CH31 Me NHMe 1Me-5-1HHz N-i-110 NA N-i-109 H NHMe 1 379 (M++1) LCMSTable-N-I-6 Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-i-111 NN1 N-i-63 CH31 CN Me NHMe 5-Bzt C 396 (M++1) N-i-112 NA N-i-1 H NHMe 5-Bzt C 382 (M++1) N-i-113 N-i-65 CHgI Me NHMe 3-Qu C 390 (M++1) N-i-114 NA N-i-113 H NHMe 3-Qu C 376 (M++1) N-i-115 N-i-67 CH31 CN Me NHMe 6-Qu C 390 (M++1) N-i-116 NA N-i-115 H NHMe 6-Qu C 376 (M++1) n N-i-117 NN1 N-i-69 CH31 ! Me NHMe 2-Nap C 405 (M++1) N-i-118 NA N-i-117 2-Nap C 391 (M++1) N-i-119 NN1 N-i-73 CH31 ! Me 408 (M++1) N-i-120 NA N-i-119 394 (M++1) N-i-121 NN1 N-i-77 CH31 Me NHMe 409 (M++1) N-i-122 NA N-i-i21 H NHMe 1Me-5-1Hldz N-i-123 N-i-79 CH31 Me NHMe 2-Nap C 403 (M++1) N-i-124 NA N-i-123 H NHMe 2-Nap C 389 (M++1) N-i-125 NN1 N-i-33 Me NHMe +1) N-i-126 NA N-i-125 H NHMe 1 Me-5-Ind 392 (M++1) N-i-i Me NHMe 1 N-i-128 NA N-i-127 H NHMe 1 393 (M++1) N-i-129 N-i-91 CH31.-CN Me NHMe 2-Nap C = V N-i-130 NA N-i-129 2-Nap C 403 (M++1) N-i-131 N-i-93 CH31 Me NHMe 1Me-5-Ind 420 (M++1) u N-i-132 H NHMe 406 (M++1) LCMSTable-N-I-7 Exp. Syn SM1 SM2 NRzRy Y Zx AR, method RTime Mass N-i-133 NN1 N-i-97 CHg N Me NHMe 1 421 (M++1) N-i-134 NA N-i-133 H NHMe 1 407 (M++1) \/ N-i-135 N-i-99 CH31 CN Me NHMe 1Me-5-Ind 420 (M++1) N-i-136 NA N-i-13b N N-i-137 N-i-103 Cl, Me NHMe 1 421 (M++1) N-i-138 NA N-i-137 CN H NHMe 1 407 (M++1) N-i-139 NN2 N-i-53 CH31 Me NMe2 2-Nap C 403 (M++1) N-i-140 NA N-i-139 H NMe2 2-Nap C = N-i-141 NN2 N-i-57 CH31 Me NMe2 1Me-5-Ind 406 (M++1) N-i-142 NA N-i-141 N H NMe2 1Me-5-Ind 392 (M++1) N-i-143 NN2 N-i-61 CH31 CN Me NMe2 1 407 (M++1) N-i-144 NA N-i-143 H NMe2 1 N-i-145 NN2 N-i-63 CH31 [N Me NMe2 5-Bzt C 410 N-i-146 NA N-i-145 H NMe2 5-Bzt C 396 (M++1) N-i-147 NN2 N-i-65 CHaI CN Me NMe2 3-Qu C 404 (M++1) N-i-148 NA N-i-147 NMe2 3-Qu C 390 (M++1) N-i-149 NN2 N-i-67 CH31 Me NMe2 6-Qu C 404 (M++1) N-i-150 NA N-i-149 CN H NMe2 6-Qu C 390 (M++1) N-i-151 NN2 N-i-69 CH31 Me NMe2 2-Nap C 419 (M++1) N-i-152 NA N-i-151 H NMe2 2-Nap C 405 405 N-i-153 NN2 N-i-73 CHj N 422 (M++1) N-i-154 NA N-i-153 H NMe2 +1) LCMS-Table-N-1-8 Exp. Syn SM1 SM2 NRzRy Method RTime Mass N-i-121 NN2 N-i-77 CH31 Me NMe2 1 423 (M++1) v _ N-i-122 NA N-i-1 H NMe2 1 409 (M++1) , N-i-123 NN2 N-i-79 CH31 Me NMe2 2-Nap C 417 (M++1) - N-i-124 NA N-i-123 23 H NMe2 2-Nap C 403 (M++1) , N-i-1 Me NMe2 1 420 (M++1) N-i-126 NA N-i-125 25 H NMe2 1 N-i-127 NN2 N-i-87 CH31 Me NMe2 421 (M++1) - N-i-128 NA N-i-127 407 (M++1) N-i-129 NN2 N-i-91 CH, Me NMe2 2-Nap C 431 (M++1) N-i-130 NA N-i-1 H NMe2 2-Nap C 417 (M++1) N-i-131 NN2 N-i-93 CH, Me NMe2 1 434 (M N-i-132 NA N-i-1 420 (M++1) N-i-133 NN2 N-i-97 CH31--CN Me NMe2 1 435 (M++1) \/ N-i-134 NA N-i-133-/N H NMe2 421 (M++1) N-i-135 N-i-99 CH35 Me NMe2 2-Nap C 431 (M++1) N-i-136 NA N-i-135 H NMe2 2-Nap C 417 (M++1) N-i-137 NN2 N-i-1 Me NMe2 lMe-5-1HMz +1) N-i-138 NA N-i-137 CN H NMe2 1 Y Zx AR LCMS[Test Examples] 1. Suppressing Action on PGEz production from IL-1 ß -stimulated MG-63 cells (1) Method for measurement An action of suppressing PGE2 production caused by interleukin (IL) 1 B as an inflammatory stimulant was studied by the following method. Cells of MG-63, which is a human osteosarcoma cell line (purchased from Dainippon Pharmaceutical), were suspended in EMEM medium (GIBCO) containing 10% fetal bovine serum (BioFluid), and then inoculated to each well of 96-well culture plate at a density of 2 x 104 cells/well and cultured overnight. The medium was changed to EMEM medium containing 0.5% fetal bovine serum, and then a test compound was added to each well. Human interleukin-1 a (ENDOGEN) was further added as an inflammatory stimulant at a final concentration of 1 ng/ml. The cells were further cultured for 18 hours. Then, the culture supernatant was collected, and the PGE2 concentration in the culture supernatant was measured by using EIA kit (CAYMAN). By using a well which was not added with the stimulant as a negative control and a well which was added only with the stimulant as a positive control, suppression ratio on PGE2 production was calculated from the produced amount of PGE2 in the well added with the test compound using the following equation.
[Equation 1] PIGEZ production suppression ratio = [1- (C-B)/ (A-B)] x 100 A: PGE2 production amount of positive control B : PGE2 production amount of negative control C : PGE2 production amount in well added with test compound Further, cytotoxicity of the compounds was studied by using the cells after the collection of the supernatant according to the methylene blue uptake method.
Specifically, the cells remained after the collection of the supernatant were fixed with glutaraldehyde and stained with a 0. 05% methylene blue solution, then methylene blue taken up by the cells was extracted with 0.3 N hydrochloric acid, and absorbance of the extract was measured at 670 nm. The absorbance of the well of the aforementioned positive control was taken as 100%, and a test compound that gave absorbance in well of less than 80% was judged to be positive in cytotoxicity.
(2) Measurement results The test compounds (Compound Nos. G-1 to G-121, H-1 to H-32, J-1 to J-92, K-1 to K-40, L-1 to L-95, M-1 to M-32, N-1 to N-74, P-1 to P-50, Q-1 to Q-52, S-1 to S-73, T-1 to T-61, U-1 to U-18, V-1 to V-109, and W-1 to W-13) suppressed the PGE2 production caused by IL-1 ß by 50% or more at 1. 0, u M. Moreover, all the test compounds did not exhibit cytotoxicity at that concentration.
The test compounds (Compound Nos. Ca-1 to Ca-203) suppressed the PGE2 production caused by IL-1 by 50% or more at 1. 0 u M. None of the test compounds exhibited cytotoxicity at that concentration.
The test compounds (Compound Nos. S-a-1 to S-a-24, S-b-1 to S-b-138, and S-c-1 to S-c-138) suppressed the PGE2 production caused by IL-1 B by 50% or more at 1. 0, u M. None of the test compounds exhibited cytotoxicity at that concentration.
Further, the test compounds (Compound Nos. N-a-1 to N-a-142, N-b-1 to N- b-182, N-c-1 to N-c-64, N-d-1 to N-d-74, N-e-1 to N-e-186 and N-g-1 to N-g-44) suppressed the PGE2 production caused by IL-1 ß by 50% or more at 1. 0, u M.
None of the test compounds exhibited cytotoxicity at that concentration.
Therefore, the novel substituted phenylalkanoic acid derivatives or salts thereof according to the present invention are useful as agents for suppressing inflammatory prostaglandin production.
2. Suppressing action on PGD2 and LTB4 production from IgE-stimulated RBL-2H3 cells (1) Method for measurement Suppressing action on PGD2 and LTB4 production caused by IgE as an allergic stimulant was investigated by the following method. Cells of RBL-2H3, which is a rat mastocytoma cell line (purchased from ATCC), were suspended in DEMEM medium (GIBCO) containing 10% fetal bovine serum (BioFluid), inoculated to each well of 48-well culture plate at a density of 2 x 104 cells/well and cultured overnight. Then, IgE antiserum directed to dinitrophenylated BSA (hereinafter abbreviated as"DNP-BSA") was further added to each well, and the cells were cultured for 30 minutes. Then, the medium was changed to DEMEM medium containing 0. 5% fetal bovine serum, a test compound was added to each well, and DNP-BSA was further added at a final concentration of 100 ng/ml as a stimulant. Ten minutes after the stimulant was added, the culture supernatant was collected, and the PGD2 concentration and LTB4 concentration in the culture supernatant were measured by using EIA kit (CAYMAN). By using a well which was not added with the stimulant as a negative control and a well which was added only with the stimulant as a positive control, suppressing ratios on mediator production were calculated from the production amounts of the mediators in the well added with the test compound using the following equation 2.
[Equation 2] PGD2 or LTB4 production suppression ratio = [1- (C-B)/(A-B)] x 100 A: PGD2 or LTB4 production amount of positive control B: PGD2 or LTB4 production amount of negative control C: PGD2 or LTB4 production amount in well added with test compound Cytotoxicity of the compounds was studied in the same manner as those described above, by using the cells after the collection of the supernatant according to the methylene blue uptake method.
(2) Measurement results Representative compounds of the objective Compounds (I) described in the specification suppressed the PGD2 and LTB4 production caused by IgE stimulation by 50% or more at 1.0 u M. Moreover, all the test compounds did not exhibit cytotoxicity at that concentration. Thus, the novel substituted phenylalkanoic acid derivatives or salts thereof according to the present invention exhibit suppressing action on the allergic prostaglandin and leukotriene production, and are useful as suppressing agents for the production thereof.
3. Suppressing effect on mouse zymosan-stimulated footpad edema reaction (1) Method for measurement A suppressing effect on footpad edema caused by zymosan as an inflammatory stimulant was studied by the following method. Groups of ICR female mice (6-to 7-week old) each consisting of eight mice were used for the test.
A test compound was suspended or dissolved in purified water containing 0. 5% methylcellulose and orally administered to the test animals at 0.1 to 500 mg/10 ml/kg. To the control group, purified water containing 0.5% methylcellulose was administered in a similar manner, which was not added with a test compound.
One hour after the administration of the test compound, 0.02 ml of a suspension of zymosan suspended in physiological saline (Otsuka Pharmaceutical) at 1 mg/ml was subcutaneously administered to right hind leg footpad of each mouse. One and two hours after the administration of the zymosan suspension, volume of the right hind leg footpad was measured by using an apparatus for measuring a volume of mouse hind leg footpad edema (Unicom). A difference of the volume of footpad measured above and the footpad volume before the administration of the test compound measured beforehand was regarded as a volume of the edema.
For the volume of the edema at 1 hour or 2 hours after the zymosan administration, a graph was prepared by indicating time in abscissa and the edema volume in ordinate, and an edema volume AUC (area under the curve) was obtained up to 2 hours by calculation using the following equation.
(Equation 31 Edema volume AUC (, u l hour) = 1/2 x 1 x A + 1 x (A + B)/2 A: Edema volume 1 hour after zymosan administration B : Edema volume 2 hour after zymosan administration A suppression ratio on edema of test compound was obtained by calculation using the following equation.
[Equation 4] Edema suppression ratio (%) = [1B/A] x 100 A: Edema volume AUC of positive control B: Edema volume AUC of test compound administered group (2) Measurement results Representative compounds of the objective Compounds (I) described in the specification more effectively suppressed footpad edema caused by subcutaneous administration of zymosan compared with the positive control group by oral administration at 0.1 to 500 mg/kg.
Therefore, the novel substituted phenylalkanoic acid derivatives or salts thereof according to the present invention exhibit a suppressing action on footpad edema caused by zymosan as an inflammatory stimulant, and thus they are useful as agents for prophylactic and/or therapeutic drugs for inflammatory diseases.
4. Suppressing effect on mouse IgE-stimulated footpad edema reaction (1) Method for measurement Suppression on footpad edema caused by IgE antibody as an allergic stimulant was studied by the following method. Groups of C57BL/6 male mice (9- to 11-week old) each consisting of five mice were used for the test. Anti-DNP-BSA IgE serum was subcutaneously administered in a volume of 20, u 1 to right hind leg footpad of each mouse one day before the test. A test compound was suspended or dissolved in purified water containing 0. 5% methylcellulose and orally administered to the test animals at 0.1 to 500 mg/10 ml/kg. To the control group, purified water containing 0. 5% methylcellulose was administered in a similar manner, which was not added with any test compound. Two hours after the administration of the test compound, 0.2 ml of a solution of DNP-BSA dissolved in physiological saline (Otsuka Pharmaceutical) at 2.5 u g/ml was intravenously administered. The thickness of right hind leg footpad was measured by using a digital thickness gauge (MITSUTOYO) 10,15, 20, and 30 minutes after the administration of DNP-BSA. A difference of the thickness of footpad measured above and the thickness before the administration of the test compound measured beforehand was regarded as a thickness of edema.
For the thickness of the edema at 10,15, 20 and 30 minutes after the DNP- BSA administration, a graph was prepared indicating time in abscissa and the edema thickness in ordinate, and edema thickness AUC up to 2 hours was obtained by calculation according to the following equation.
Equation 5] Edema thickness AUC (mm minute) = 1/2 x 10 x A + 5 x (A + B)/2 + 5 x (B + C)/2 + 10 x (C + D)/2 A : Edema thickness 10 minutes after DNP-BSA administration B : Edema thickness 15 minutes after DNP-BSA administration C: Edema thickness 20 minutes after DNP-BSA administration D: Edema thickness 30 minutes after DNP-BSA administration A suppressing ratio on edema of a test compound was obtained by calculation in accordance with the following equation.
[Equation 6] Edema suppression ratio (%) = [1 - B/A] x 100 A: Edema thickness AUC of positive control B: Edema thickness AUC of test compound administered group (2) Measurement results Representative compounds of the objective Compounds (I) described in the specification suppressed the footpad edema caused by IgE stimulation, i. e. , footpad edema observed when DNP-BSA was administered to the mice sensitized with the anti-DNP-BSA IgE serum, compared with the positive control group by oral administration of 0.1 to 500 mg/kg.
Therefore, the novel substituted phenylalkanoic acid derivatives or salts thereof according to the present invention exhibit suppressing action on footpad edema caused by IgE antibody, which is an allergic stimulant, and thus they are useful as prophylactic and/or therapeutic drugs for allergic diseases.
5. Suppressing effect on mouse acetic acid writhing reaction (1) Method for measurement A suppressing effect on acetic acid writhing reaction, which is an acute pain model, was studied by the following method. Groups of ICR female mice (6-week old) each consisting of eight mice were used for the test. A test compound was suspended or dissolved in purified water containing 0.5% methylcellulose and orally administered to the test animals at 0.1 to 500 mg/10 ml/kg. To the control group, purified water containing 0. 5% methylcellulose was administered in a similar manner, which was not added with any test compound. One hour after the administration of the test compound, 0.9% aqueous acetic acid was intraperitoneally administered to the mice in a volume of 5 ml/kg, and number of writhing reactions during 15 minutes immediately after the administration of acetic acid was counted. Suppression ratio relative to the control group was obtained by calculation according to the following equation.
[Equation 7] Writhing suppression ratio (%) = [1-B/A] x 100 A : Writhing number of positive control group B : Writhing number of test compound administered group (2) Measurement results The representative compounds of the objective Compounds (I) described in the specification suppressed writhing caused by administration of aqueous acetic acid compared with the positive control group at oral administration of 0.1 to 500 mg/kg.
It has been elucidated that a writhing reaction caused by intraperitoneal administration of acetic acid is caused due to production of prostaglandin [Matsumoto et al. , European Journal of Pharmacology (Eur. J. Pharmacol), 1998, vol. 352, p. 47 ; Ueno et al., Biochemical Pharmacology (Biochem. Pharmacol), 2001, vol. 15, p. 157].
Therefore, the novel substituted phenylalkanoic acid derivatives or salts thereof according to the present invention are useful as prophylactic and/or therapeutic agents for acute pain caused by prostaglandins.
6. Prophylactic and therapeutic effects for rat adjuvant arthritis (1) Method for measurement A suppressing effect on footpad edema observed in rat adjuvant arthritis, which is a disease model of rheumatoid arthritis as being one of autoimmune diseases and also a chronic inflammatory disease, was studied by the following method. Groups of Lewis female rats (8-week old) each consisting of six mice were used for the test. The test animals were immunized by subcutaneously administering, to right hind leg footpads, 50, u 1 of liquid paraffin containing 10 mg/ml of M. tuberclulosis H37 RA (DIFCO) as an adjuvant. A test compound was suspended or dissolved in purified water containing 0.5% methylcellulose and orally administered to the test animals at 0.1 to 500 mg/5 ml/kg. The test compound was administered twice a day for 14 days, from the 12th day after the immunization.
To the control group, purified water containing 0.5% methylcellulose was administered in a similar manner, which was not added with any test compound.
Every 2 or 3 days after the administration of adjuvant, volume of left hind leg footpad, which was not administered with the adjuvant, was measured by using an apparatus for measuring a volume of edema of a rat hind leg footpad (Unicom). A suppression ratio on edema was obtained by calculation using the following equation.
[Equation 8] Edema suppression ratio 11- [ (D-C)/C]/ [ (B-A)/All x 100 A: Left hind leg footpad volume of positive control immediately before administration of adjuvant B: Left hind leg footpad volume of positive control on each measurement day C: Left hind leg footpad volume of test compound administered group immediately before administration of adjuvant D : Left hind leg footpad volume of test compound administered group on each measurement day (2) Measurement results The representative compounds of the objective Compound (I) described in the specification suppressed footpad edema in adjuvant arthritis compared with the positive control group.
Therefore, the novel substituted phenylalkanoic acid derivatives or salts thereof according to the present invention are useful as agents for prophylactic and/or therapeutic drugs for rheumatoid arthritis and autoimmune diseases.
7. Effect on rat pulmonary fibrosis (1) Method for measurement A suppressing effect on pulmonary fibrosing in a bleomycin-induced rat pulmonary fibrosis model, which is a pathological model of pulmonary fibrosis, was studied by the following method. Groups of BN female rats (7-week old) each consisting of seven rats were used for the test. The test animals were anesthetized with ketamine and xylazine, and the tracheae were exposed. Then, a 125, u g/0.1 ml solution of bleomycin (Nippon Kayaku) dissolved in physiological saline (Ohtsuka Pharmaceutical Factory) was injected into the tracheae by using a syringe. The negative control group was administered with 0.1 ml of saline into the tracheae.
Each test compound was suspended or dissolved in purified water containing 0.5% methylcellulose, and orally administered to the test animals at doses of 10,30, 100 and 300 mg/5 ml/kg. The administration of the test compounds was started from the day of the bleomycin administration and performed once or twice a day for 21 days. The positive control group was administered with purified water containing 0.5% methylcellulose not added with any test compound in a similar manner. On the 21st day after the administration of bleomycin, the rats were sacrificed, and lungs were fixed with neutral buffered formalin to prepare histopathological samples. Staining of the histopathological samples was performed by the Azan method.
The histopathological samples of lungs were examined, and degree of fibrosing was represented with the following scores on the basis of formation of granulation tissues and proliferation of collagen fibers as indicators, i. e.,- : no abnormality, i : extremely mild change, +: mild change, ++: moderate change, and +++ : significant change.
(2) Measurement results The fibrosing score of the negative control group was minus (-), and no pulmonary fibrosing was observed. The median of the fibrosing score of the positive control group was from ++ to +++, and pulmonary fibrosing was observed.
The medians of the fibrosing score of the groups of rats administered with the test compounds (Compound Nos. G-2, G-4 and V-40) were from to +, and thus the fibrosing was milder compared with the positive control group. The median of the fibrosing score of the group administered with the other test compounds (Compound Nos. G118 and V-59) was from to +, and thus pulmonary fibrosing was milder that that observed in the positive control group. Accordingly, the compounds of the present invention are useful as a prophylactic and/or therapeutic agent for pulmonary fibrosis, and type 4 PLA2 inhibitor compounds are useful as a prophylactic and/or therapeutic agent (including a progression-preventing agent) for pulmonary fibrosis.
Further, known cPLA2 inhibitory compounds, arachidonyl trifluoromethyl ketone, 4-(1-benzhydryl-6-chloro-lH-indol-3-ylmethyl)-3-methoxybenzo ic acid, N-{1- [2- (2,4-difluorobenzoyl) benzoyl]-4-tritylsulfanylpyrrolidin-2-ylmethyl}-4- (2,4- dioxothiazolidin-5-ylidenemethyl) benzoic acid amide and 4- {4- [2- (2- [bis (4- chlorophenyl) methoxy] ethylsulfonyl) ethoxy] phenyl}-1, 1, 1-trifluoro-2-butanone, are intraperitoneally or orally administered in a similar manner. Fibrosing is mild also in the groups administered with these known type 4 PLA2 inhibitory compounds.
Industrial Applicability The compounds of the present invention have superior suppressing action on prostaglandin production and leukotriene production, and they are useful as active ingredients of medicaments for prophylactic and/or therapeutic treatment of various inflammatory diseases, autoimmune diseases, allergic diseases, pain, fibrosis and the like caused by these lipid mediators.
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