TECHNICAL FIELD The present invention relates to a novel urea derivative represented by the following formula (I), which is useful as an anti-cancer agent: , its pharmaceutically acceptable acid addition salt or stereoisomer, in which X represents O or S, or represents imino substituted or unsubstituted by cyano, Y represents a direct bond, NH, 0 or S, B represents C,-Cs-alkyl, or represents a radical having one of the following formulas: wherein R'and R2 independently of one another represent hydrogen, C,-C-alkyl or cyano, or represent amidino substituted or unsubstituted by C,-C8-alkyl, Q represents CH or N, Z represents C,-C4-alkoxy or phenoxy, n represents an integer of 0 to 3, R3, R4, R5, R6 and R'independently of one another represent hydrogen, C,-C8-alkyl or halogen, Het represents a radical having one of the following formulas:

wherein R8, R9, R10, R11 and R12 independently of one another represent hydrogen, C1-C8-alkyl, Cl- Alkoxy or halogen, R'3 and R'4 independently of one another represent hydrogen, C,-C8-alkyl, C,-C8-alkoxy, C2-C5-alkenyl, C3-C6-cycloalkyl or C3-C6-cycloalkyl-C,-C4-alkyl, or R'3 and R'4 together with the nitrogen atom to which they are attached represent pyrrolinyl or pyrrolidinyl, R"represents hydrogen, or represents phenyl or benzyl each of which is substituted or unsubstituted by 1 to 5 identical or different halogen atoms, R 16 and R17 independently of one another represent hydrogen, C1-C4-alkyl, C1-C4-alkoxy or hydroxy, R'8 and R'9 independently of one another represent hydrogen, hydroxycarbonyl or C1-C4-1 alkoxycarbonyl, or represent phenyl substituted or unsubstituted by 1 to 5 identical or different halogen atoms or Cl-C4-alkoxy, or together represent diphenylmethylene or benzolactone of formula

R 20 and R 21 independently of one another represent hydrogen, or represent phenyl substituted or unsubstituted by 1 to 5 identical or different halogen atoms, C,-C8-alkyl or C,-C4-alkoxy, or represent C,-C4-alkoxycarbonyl.

The present invention also relates to a process for preparing the compound of formula (I), and an anti-cancer composition comprising the compound of formula (1) as an active ingredient.

BACKGROUND ART As anti-cancer agents, cisplatin, doxorubicin (adriamycin), 5-FU, camptothecin, taxol, etc. are currently known and used clinically. One of platinum complex as anti-cancer agents, cisplatin, shows its activity based on the DNA alkylation reaction. But, it is not freed from severe side effects and toxicity due to the heavy metal. Further, as anti-cancer agents such as doxorubicin (adriamycin), etc., which show their activity through the intercalation mechanism, have lower selectivity, they could also lead to these adverse and undesirable effects. Meanwhile, the taxol derivative, which has been recently developed and proved an effective weapon against breast, ovarian, lung cancer, etc., requires a special formulation because it is sparingly soluble in water. Therefore, severe side effects may also be caused by the use of the excipients required for the formulation.

For these reasons, it has been needed to develop a new anti-cancer agent which can realize a superior anti-cancer activity as well as overcome the problems (low selectivity against the solid tumors in human body, low solubility in water, side effects, toxicity, etc.) aligned to the existing agents.

DISCLOSURE OF INVENTION

Thus, the present inventors have extensively studied to minimize the problems of the existing anti-cancer agents, and to develop a new compound having a potent and effective anti-cancer activity against the solid tumors in human body. As a result, we have identified that the urea derivative of formula (I) above meets the requirements of potent anti-cancer activity and low toxicity, and then completed the present invention.

Therefore, the object of the present invention is to provide the urea derivative of formula (I), as defined above, its pharmaceutically acceptable salt and stereoisomer.

It is another object of the present invention to provide a process for preparing the compound of formula (I).

It is still another object of the present invention to provide an anti-cancer composition having a superior physiological activity against solid cancers in human body and a low toxicity comprising the compound of formula (I) as an active-ingredient together with a pharmaceutically acceptable carrier.

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a novel urea derivative represented by the following formula (I), which shows a superior anti-cancer activity and a low toxicity:

, its pharmaceutically acceptable acid addition salt or stereoisomer, in which X represents O or S, or represents imino substituted or unsubstituted by cyano, Y represents a direct bond, NH, O or S, B represents C,-C8-alkyl, or represents a radical having one of the following formulas:

wherein R1 and R2 independently of one another represent hydrogen, C,-C8-alkyl or cyano, or represent amidino substituted or unsubstituted by C1-C8-alkyl, Q represents CH or N, Z represents Cl-C4-alkoxy or phenoxy, n represents an integer of 0 to 3, R3, R4, R5, R6 and R'independently of one another represent hydrogen, Cl-C$-alkyl or halogen, Het represents a radical having one of the following formulas :

wherein R8, R9, R'°, R"independently of one another represent hydrogen, Cl-Cg-alkyl, Cl- Alkoxy or halogen, R13 and R14 independently of one another represent hydrogen, C1-C8-alkyl, C1-C8-alkoxy, C2-C5-alkenyl, C3-C6-cycloalkyl or C3-C6-cycloalkyl-Cl-C4-alkyl, or R'3 and R'4 together with the nitrogen atom to which they are attached represent pyrrolinyl or pyrrolidinyl, R15 respresents hydrogen, or represents phenyl or benzyl each of which is substituted or unsubstituted by 1 to 5 identical or different halogen atoms, R'6 and R"independently of one another represent hydrogen, C1-C4-alkyls, C1-C4-alkoxy or hydroxy, R'8 and R19 independently of one another represent hydrogen, hydroxy'carbonyl or C1-C4- alkoxycarbonyl, or represent phenyl substituted or unsubstituted by 1 to 5 identical or different halogen atoms or C,-C4-alkoxy, or together represent diphenylmethylene or benzolactone of formula WO and R21 independently of one another represent hydrogen, or represent phenyl substituted or unsubstituted by 1 to 5 identical or different halogen atoms, Cl-C8-alkyl or Cl-C4-alkoxy, or represent C1-C7-alkoxycarbonyl.

In the definitions for the substituents of the compound of formula (I), the term "alkyl"used alone or in a composite term such as"alkoxy"means a straight-chain or

branched saturated hydrocarbon radical such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl and t-butyl, etc.; the term"alkenyl"means an unsaturated hydrocarbon radical having one or more double bonds therein such as ethenyl, propenyl, butenyl, etc.; the term"cycloalkyl"means cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; the term "alkoxycarbonyl"means methoxycarbonyl, ethoxycarbonyl, etc.; and the term"halogen" means fluorine, chlorine, bromine or iodine.

Typical examples of the compound of formula (I) according to the present invention are represented in the following Table 1 : Table la No. B Y X R1'Rib Rrr V/==\ N OMe N oye 1 { z o oM oM zon OMe N : C 3; \ N NH O 4Me OiIe 2 FT 1 H 0--} OMe OMe ! T. t-ri< "N OMe 3! {T T"NH 0-f)'OMe OMe N OMe N W SNX NH O *W OMe OMe N OMe nez I 5 NH 0 F OMe OMe N orme 0 N mye 6 NH 0 OMC Ome nome I NH 0 OMe OMe omet, t

Table la (continued) No. _-_ _ _ ... _ No. i N-rOPh , """" ; N OPh s I rx o aM o i i v i a i 10 NH 0 F OMe OMe .... _ NH 0 f __,-_ i f ; . i . O c OMe OMe, i Table 1b No. B Y X R"R'" _ b 3--- N OMe 13 NH 0 12 , (NH O N OMe 0 f.. _..... __-' I I 1 13 NH O N OMe ...., N 'H"OMe N OMe'____. __... _. i NH O Ph e Ph -C NH 0 N I OMe i i 17 NH 0 Ph Ph . _ 17 > NH O Ph Ph Table lb (continued) 1 No. g B I Y X R'R1w I Q i' i ; /\ ; ; I 18 S NH O COOH Ph '1 ) t 19 NH o COOH Ph N OMe 1 'N OMe i <\ o o i eooH Pn i a i 2 N 0 COOH Ph 21 i NH U ; N OMe;' 21 1 NH i j r N\ i i o ; a o N OMe i I' 22 nu Table 1c No. B Y X D !. 1/ 23 NH 0 N Oye 24 NH N-CN N OMe i N N N OMe N-= N- nome /\ .......... N OMe ! ..------------------ 28 aNf i J cl 'nu 0 I I'/\ ! [LJL 1 I O Table le (continued) o- - No. B | Y X D i : ; t' : i i w ! 0 O QX i ° i \/ 31 NH 0 i"' 33 s 1 I I I I 32 NH O O ij O X 33 I N. C S . \ 34)-NH 0- I NJ Q N= ( I ! i i Table le (continued) B Y X _... _. __. __. D No. B y x D ; I '== ( 35 ; .-Q'l i i i 36 NH 0 38 i I zu ; 39 nu y\ !)- 0. . __./\ __ _ __ , '3 g ()--N N J i r v 39 NH 4--N 1

Table le (continued) No. B Y X D I \ N ; 4o rrt o- N- nu N _ _____ ) Nt 0J i --_. _ I 0s . ! i N-- ! 1 i' a i rr = 43 NH N-CN U __ t_. , i N 44 NH N-CN N-N-. i H

Table Ic (continued) No. B y lfl \N : ; u =C 0--CN N H N 4 nu PN OMe NtN < Zu ... i N 46 NH--<\ N Oye ! N : nu 0 i i i 1 f N OMe ni i ' t0 49 t tt j NH 0- ( 49 NH I N OEt N OE ; + O Table Ic (continued) No. B Y X D zu _. _ nu N 5, 1 5a , : . Qrn \/ 51 tj! jr NH 0-. N N :-Come N NH 0 a N N NH 53 '11 OMe N _ wo H. N'j F , ß NA i'_.. Airect /\ 53 () ( J NH 0- N 'NOM. i bond 7 I Table ld No. ; B _ X _ _ ___ __ _ HQt-_ 55 NtN ° NUN XMe Me 5 6 Nl<\N _ S NUN XMe No.B x Het Me me SS N- Me mye Me 57 N-S- mice MYE ! 58 N-0--C 1 hot Me H i ORME N N i N/\-/ OMe N 59 f N N f H NEZ 60 Jrr-, S _ 60 N-N\2 H Table ld (continued) No. B x Het {... I 'I. i s/ N 1\ Na Nu i i 61'N-0-N N- N N N H N N N-=.. C I " NEZ N 63 N N -J N= TU 'I 65 Nl+\N o N\N >N < NL nez ' u, ! ! 0 65 /-0-C 0

Table ld (continued) No. B X Het 66 0 ome -d OMe 67 oye Nez oye N 67 N-'S , OMe N 68 oye N oye ; l /OMe N --OMe -. N i 69 N /oMe Me F 70 N-0 OMe N oye lxome I.. _. __

Table Id (continued) 8 No. B X Het ci i 73 Nsc/i 7 o HOMO -N oye --N'JJ « I t N OMe F C1 , OMe Cl -N cul 74 N-0 N oye 75 N-0 Table ld (continued) No. X Het 7ó N < O $ 77 {Nl) F i : ; r 76 rr- ci nid ci cri XI -OH zizi -N -oh \ 7 out i N \ I -.-,. OH out ! i \/ 7'N d OEt N 1 i 81 s-N J. I Table ld (continued) No. B X Het .,.., o -N 0 i 0 HOMO orme i, _ o _ oye ; Ulvie i i 1.. --N N 1 N 1/N. J 0 U 1 l j i N-0 i i s ---I o w NH N- s I ;

Also, the compound of formula (I) according to the present invention can form a pharmaceutically acceptable acid addition salt. Such acid addition salt includes non-toxic

acid addition salt containing pharmaceutically acceptable anion, for example a salt with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydriodic acid, etc., a salt with organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, propionic acid, trichloroacetic acid, trofluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, etc., or a salt with amino acids such as serine, cystine, cystine, aspartic acid, glutamic acid, lysine, arginin, tyrosine, proline, etc., or a salt with sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc.

Since the compounds of the present invention may have asymmetric carbon center (s) depending on the kind of substituents, they can exist as an enantiomer of R or S, diastereomer, or mixtures thereof including racemate. Therefore, the present invention also includes each of these stereoisomers and their mixtures.

Another object of the present invention is to provide a process for preparing the compound of formula (I) as defined above.

According to the present invention, the compound of formula (I), as defined above, can be prepared by a process characterized in that (a) a compound represented by the following formula (II) : B-YH an wherein B and Y are as defined above, and a compound represented by the following formula (III) :

wherein X is as defined above, and L represents a leaving group, preferably Cl-c4- alkoxy, phenoxy, p-toluenesulfonyl, benzenesulfonyl, p-nitrosulfonyl, halogen or imidazole, are reacted in a solvent in the presence of a base with a compound represented by the following formula (IV): H-Het (IV) wherein Het is as defined above, to produce the compound of formula (I); or (b) a compound represented by the following formula (V) : wherein B, Y, X and L are as defined above, is reacted in a solvent in the presence of a base with the compound of formula (IV) to produce the compound of formula (I) ; or (c) a compound represented by the following formula (VI) : wherein X is as defined above, is reacted in a solvent in the presence of a base with the compound of formula (IV) to produce a compound represented by the following formula (Ida):

wherein X and Het are as defined above, or optionally deprotection, alkylation or esterification reaction is further carried out.

The above process variants (a) to (c) can be depicted as follows.

Reaction Scheme 1 Solvent B-YH + t + H-Het (TII) IJ (zv3 Base Reaction Scheme 2 x ! ! Solvent BY L + HHet > (I) (V) on base Reaction Scheme 3 x Solvent e NUN + M-Het----- (Ida) Base tVi) (i) In the process variant (a), the compounds of formulae (II) and (IV) are commercially available, or may be prepared according to the art-known methods (see: J.

Med. Chem., 35,3792 (1992), USP 4.011,319). Several compounds having the formula (III) have been known and any one selected from phosgene, liquid and solid phosgene,

thiophosgene, 1, 1'-carbonyldiimidazole, 1, 1'-thiocarbonyldiimidazole, diphenylcarbonate, diphenylthiocarbonate, chloromethylformate, chloroethylformate, and chlorophenyl- formate can be preferably used in the present invention. In order to prepare N- cyanocarbo-imidate, diphenyl N-cyanocarboimidate can be used.

The compound of formula (II) can be preferably used in an amount of 0.5 to 2 equivalents with respect to the compound of formula (IV), and the compound of formula (III) can be preferably used in an amount of 0.5 to 3 equivalents with respect to the same compound of formula (IV).

Any solvent which does not adversely affect to the reaction, preferably one or more selected from a group consisting of methylene chloride, chloroform, tetrahydrofuran, acetonitrile and dimethylformamide, more preferably a solvent having a comparatively high polarity such as tetrahydrofuran or dimethylformamide can be used.

Any conventional organic or inorganic base can be used. The preferable inorganic base includes sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate and cesium carbonate, and the preferable organic base includes trimethylamine, triethylamine, tributylamine, pyridine, dimethylaminopyridine, DBU, and DBN. The base can be used in an amount of 1 to 3 equivalents with respect to the compound of formula (IV).

The reaction is preferably carried out at temperatures ranging from 20 to 100°C.

In process variant (b), the starting compound of formula (V) is commercially available, or may be easily prepared by reacting the compound of formula (II) with the compound of formula (III). The compound of formula (V) can be preferably used in an amount of 0.5 to 2 equivalents with respect to the compound of formula (IV).

The same solvents and bases mentioned for process variant (a) can be used in process variant (b), and the reaction temperature can be selected from the same range. l, 1'-Carbonyldiimidazole or 1, 1'-thiocarbonyldiimidazole of formula (VI), used in process variant (c), is commercially available. The compound of formula (VI) can be used in an amount of 0.5 to 2 equivalents with respect to the compound of formula (IV).

The same solvents and bases mentioned for process variant (a) can be used in process variant (c), and the reaction temperature can be selected from the same range.

The reaction time may be generally selected from a range of from 0.5 to 48 hours.

The compound of formula (I) prepared according to the process as explained above can be effectively used as an anti-cancer agent as already mentioned. Therefore, the present invention also provides an anti-cancer composition comprising as an active ingredient the compound of formula (I), its pharmaceutically acceptable acid-addition salt, or stereoisomer, together with a pharmaceutically acceptable carrier.

When the active compound according to the present invention is used for clinical purpose, it is preferably administered in an amount ranging from 1 to 1000mg per kg of body weight a day. The total daily dosage may be administered in one time or over several times. However, the specific administration dosage for the patient can be varied with the specific compound used, body weight of the subject patient, sex, hygienic condition, diet, time or method of administration, excretion rate, mixing ratio of the agent, severity of the disease to be treated, etc.

The compound of the present invention may be administered in the form of injections or oral preparations. Injections, for example, sterilized aqueous or oily suspension for injection, can be prepared according to the known procedure using suitable carriers. Solvents which can be used for preparing injections include water, Ringer's fluid

and isotonic NaCl solution, and also sterilized fixing oil may be conveniently used as the solvent or suspending media. Any non-stimulative fixing oil including mono-, di- glyceride may be used for this purpose. Fatty acid such as oleic acid may also be used for injections.

As the solid preparation for oral administration, capsules, tablets, pills, powders and granules, etc., preferably capsules and tablets can be mentioned. It is also desirable for tablets and pills to be formulated into enteric-coated preparation. The solid preparations may be prepared by mixing the active compound of formula (I) according to the present invention with at least one inert carriers.

The pharmaceutically acceptable carriers which can be used for preparing the pharmaceutical composition of the present invention include dispersing agent, wetting agent, suspending agent, lubricant, sweetening agent, binding agent, solubilizer, solubilizing aid, emulsifier, isotonizing agent, adsorbent, disintegrating agent, antioxidant, preservative, glidant, filler, fragrant, etc., more specifically lactose, dextrose, sucrose, starch, mannitol, sorbitol, cellulose, glycine, silica, talc, stearic acid, stearine, tragacanth gum, methyl cellulose, sodium carboxylmethylcellulose, agar, magnesium stearate, alginic acid, water, ethanol, polyethyleneglycol, polyvinylpyrrolidone, sodium chloride, potassium chloride, orange essence, strawberry essence, vanilla, etc.

The present invention, particularly the preparing process and pharmacological effect as explained above, will be more specifically explained in the following examples and experimentals. However, it should be understood that the following examples and experimentals are intended to illustrate the present invention but not in any manner to limit the scope of the present invention.

Example 1 Synthesis of 3-ion- (5,6-dimethyl-2-methoxypyridin-3-yl) aminocarbonyl]-7, 8-

dimethoxy-l-phenyl-2, 3,4,5-tetrahydro-3H-benzazepine N- (5, 6-dimethyl-2-methoxypyridin-3-yl) phenylcarbamate (71mg, 0.26mmol) and 7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-3H-benzazepine (67.2mg, 0.28mmol) were mixed in anhydrous THF (5m#), and then DBU (39, tt. , 0.26mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50mßx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 89.6mg (Yield 81.8%) of the title compound as a solid. m. p. : 88-90 °C 1H NMR(300MHz, CDCl3) : # ppm 7.14-7.34 (m, 5H), 6.79 (s, 1H), 6.66 (s, 1H), 6.45 (s, 1H), 4.58 (dd, 1H, J=10.06Hz, J=5.64Hz), 4.24 (dd, 1H, J=14.94Hz, J=5.58Hz), 3,93 (s, 3H), 3.88 (s, 3H), 3.60-3.95 (m, 3H), 3.67 (s, 3H), 3.39 (m, 1H), 2.89 (m, 1H), 2.32 (s, 3H), 2. 16 (s, 3H) Example 2 Synthesis of 3- [N- (2-methoxyquinoxalin-3-yl) aminocarbonyl]-7, 8-dimethoxy- 1-phenyl-2,3,4,5-tetrahydro-3H-benzazepine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (3.4g, 10.17mmol) and 7,8- dimethoxy-l-phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (3.26g, 10.17mmol) were mixed in anhydrous THE (57mA), and then DBU (1. 7m#, 10.17mmol) was added dropwise to this reaction solution. After stirring for 1 hour at room temperature, the product was extracted with methylene chloride (200m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 3.69g (Yield 66.1%) of the

title compound as a solid. m. p.: 96-98°C 'H NMR (300MHz, CDCl3) : # ppm 6.49-7.83 (m, 12H), 4.60 (m, 1H), 4.30 (m, 1H), 4.11 (s, 3H), 3.88 (m, 5H), 3.70 (m, 4h), 3.30 (m, 1H), 2.86 (m, 1H) Example 3 Synthesis of 3-[N-(2-methoxyquinoxalin-3-yl) aminocarbonyl]-(S)-7, 8- dimethoxy-l-phenyl-2,3,4,5-tetrahydro-3H-benzazepine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (112.1mg, 0.38mmol) and (S)-7,8- dimethoxy-1-phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (107.6mg, 0.38mmol) were mixed in anhydrous THF (2m3), and then DBU (70µ#, 0.47mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with methylene chloride (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent : ethyl acetate: hexane=2: 3, v/v) to give 41.3mg (Yield 24.1%) of the title compound as a solid. m. p.: 143-144°C 'H NMR. (500MHz, CDCl) : 8 ppm 6.49-7.83 (m, 12H), 4.60 (m, 1H), 4.30 (m, 1H), 4.11 (s, 3H), 3.88 (m, 5H), 3.70 (m, 4H), 3.30 (m, 1H), 2.86 (m, 1H) Example 4 Synthesis of 3- [N- (2-methoxyquinoxalin-3-yl) aminocarbonyl]- (R)-7, 8- dimethoxy-l-phenyl-2,3,4,5- tetrahydro-3H-benzazepine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (100mg, 0.34mmol) and (R)-7,8- dimethoxy-l-phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (95.9mg, 0.34mmol) were mixed in anhydrous THF (2m#), and then DBU (70, 0. 47mmol) was added dropwise to this

reaction solution. After stirring for 1 hour at room temperature, the product was extracted with methylene chloride (50maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2: 3, v/v) to give 124.7mg (Yield 81.7%) of the title compound as a solid. m. p.: 92-94°C 'H NMR (50OMHz, CDCl3) : 6 ppm 6.48-7.82 (m, 12H), 4.60 (m, 1H), 4.30 (m, 1H), 4.11 (s, 3H), 3.88 (m, 5H), 3.70 (m, 4H), 3.30 (m, 1H), 2.86 (m, 1H) Example 5 Synthesis of 3-[N-(2-methoxyquinoxalin-3-yl) aminocarbonyl]-7, 8-dimethoxy- 1- (4-fluoro) phenyl-2,3,4,5-tetrahydro-3H-benzazepine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (100mg, 0.34mmol) and 7,8- dimethoxy-l- (4-fluoro) phenyl-2,3,4,5-tetrahydro-3H-benzazepine (101.7mg, 0.34 mmol) were mixed in anhydrous THF (2mA), and then DBU (70, 0. 47mmol) was added dropwise to this reaction solution. After stirring for 1 hour at room temperature, the product was extracted with methylene chloride (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2 : 3, v/v) to give 109. 9mg (Yield 69.2%) of the title compound as a solid. m. p.: 96-98°C 'H NMR (50OMHz, CDCl3) : 8 ppm 6.46-7.81 (m, 11H), 4.59 (m, 1H), 4.25 (m, 1H), 4.12 (s, 3H), 3.88 (m, 5H), 3.72 (m, 4H), 3.31 (m, 1H), 3.21 (m, 1H), 2.85 (m, 1H) Example 6 Synthesis of 3- »-(2-methoxyquinoxalin-3-yl) aminocarbonyl]-7S8-dimethoxy-

1- (4-chloro) phenyl-2,3,4,5-tetrahydro-3H-benzazepine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (35.3mg, 0.12mmol) and 7,8- dimethoxy-1- (4-chloro) phenyl-2,3,4,5-tetrahydro-3H-benzazepine (38. Omg, 0.12mmol) were mixed in anhydrous THE (0. 6mA), and then DBU (20ut, 0.13mmol) was added dropwise to this reaction solution. After stirring for 1 hour at room temperature, the product was extracted with methylene chloride (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2 : 3, v/v) to give 20.4mg (Yield 32.8%) of the title compound as a solid. m. p.: 94-97°C 'H NMR (50OMHz, CDCl3) : 6 ppm 6.46-7.47 (m, 11H), 4.54 (m, 1H), 4.20 (m, 1H), 4.12 (m, 3H), 3.88 (m, 5H), 3.72 (m, 4H), 3.25 (m, 1H), 2.86 (m, 1H) Example 7 Synthesis of 3-[N-(2-ethoxyquinowalin-3-yl) aminocarbonyl]-7, 8-dimethoxy-1- phenyl-2, 3,4,5-tetrahydro-3H-benzazepine N- (2-ethoxyquinoxalin-3-yl) phenylcarbamate (100mg, 0.32mmol) and 7,8- dimethoxy-l-phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (90.5mg, 0.32mmol) were mixed in anhydrous THF (2mut), and then DBU (700, 0.47mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with methylene chloride (50maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2: 3, v/v) to give 109.5mg (Yield 68.7%) of the title compound as a solid. m. p. : 136-138 °C

'H NMR (500MHz, CDCl3) : 8 ppm 6.47-7.80 (m, 12H), 4.65 (m, 1H), 4.58 (q, 2H) 4.35 (m, 1H), 3.88 (m, 4H), 3.78 (m, 2H), 3.70 (s, 3H), 3.30 (m, 1H), 2.88 (m, 1H), 1. 46 (t, 3H) Example 8 Synthesis of 3-[N-(2-phenoxyquinoxalin-3-yl) aminocarbonyl]-7, 8-dimethoxy- 1-phenyl-2,3,4,5-tetrahydro-3H-benzazepine N- (2-phenoxyquinoxalin-3-yl) phenylcarbamate (50mg, 0. 14mmol) and 7,8- dimethoxy-l-phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (39.6mg, 0. 14mmol) were mixed in anhydrous THF (0. 7m#), and then DBU (30µ#, 0. 20mmol) was added dropwise to this reaction solution. After stirring for 1 hour at room temperature, the product was extracted with methylene chloride (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2: 3, v/v) to give 21.6mg (Yield 28.4%) of the title compound as a solid. m. p. : 108-110°C 'H NMR (500MHz, CDCl3) : # ppm 6.48-7.85 (m, 15H), 4.60 (m, 1H), 4.30 (m, 1H), 3.87 (m, 5H), 3.80 (m, 1H), 3.69 (s, 3H), 3.30 (m, 1H), 2.88 (m, 1H) Example 9 Synthesis of 3-[N-(diphenylmethyl) aminocarbonyl]-7, 8-dimethoxy-1-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine N- (diphenylmethyl) phenylcarbamate (94.2mg, 0.31mmol) and 7,8-dimethoxy-1- phenyl-2,3,4,5-tetrahydro-3H-benzazepine (80mg, 0.28mmol) were mixed in anhydrous THF (5mu), and then DBU (45. 6 : Q, 0. 30mmol) was added dropwise to this reaction solution.

After stirring for 3 hours at room temperature, the product was extracted with ethyl

acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 106mg (Yield 76.3%) of the title compound as a solid. m. p.: 155-158°C 'H NMR (300MHz, CDCl3) : 6 ppm 7. 01-7.30 (m, 15H), 6.66 (s, 1H), 6. 40 (s, 1H), 6.01 (d, 1H, J=6.86Hz), 4.74 (d, 1H, J=6.86Hz), 4.51 (dd, 1H, J=8.61Hz, J=5.31Hz), 3.89 (s, 3H), 3.69 (s, 3H), 3.53-3.84 (m, 3H), 3.22 (m, 1H), 2.84 (m, 1H) Example 10 Synthesis of 3-[N-(diphenylmethyl)aminocarbonyl]-7,8-dimethoxy--1-(4- fluoro) phenyl-2, 3,4,5-tetrahydro-3H-benzazepine N- (diphenylmethyl) phenylcarbamate (51.7mg, 0. 17mmol) and 7,8-dimethoxy-1- (4- fluoro) phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (51.4mg, 0. 17 mmol) were mixed in anhydrous THF (4nLQ), and then DBU (25.5, me, 0.17mmol) was added dropwise to this reaction solution. After stirring for 18 hours at room temperature, the product was extracted with ethyl acetate (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 54.4mg (Yield 62.5%) of the title compound as a solid. m. p.: 187-188°C 'H NMR (300MHz, CDC13) : 6 ppm 6.88-7.30 (m, 14H), 6.66 (s, 1H), 6.44 (s, 1H), 6.02 (d, 1H, J=6.85Hz), 4.72 (d, 1H, J=6.85Hz), 4.48 (t, IM, 4.07 (m, 1H), 3.89 (s, 3H), 3.71 (s, 3H), 3.61-3.85 (m, 2H), 3.55 (m, 1H), 3.20 (m, 1H), 2.86 (m, 1H) Example 11 Synthesis of 3- [N- (diphenylmethyl) aminocarbonyl]-7, 8-dimethoxy-1- (4-

chloro) phenyl-2, 3,4,5-tetrahydro-3H-benzazepine N- (diphenylmethyl) phenylcarbamate (56.4mg, 0.19mmol) and 7,8-dimethoxy-1- (4-chloro) phenyl-2,3,4,5-tetrahydro-3H-benzazepine (59.1mg, 0.19 mmol) were mixed in anhydrous THE (3mut), and then DBU (27.8, ct, 0.19mmol) was added dropwise to this reaction solution. After stirring for 16 hours at room temperature, the product was extracted with ethyl acetate (30mEx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 75.9mg (Yield 77.5%) of the title compound as a solid. m. p.: 205-207°C 'H NMR (300MHz, CDC13) : 6 ppm 6.99-7.30 (m, 14H), 6.66 (s, IM, 6. 44 (s, 1H), 6.02 (d, 1H, J=6.86Hz), 4.74 (d, 1H, J=6.86Hz), 4.48 (dd, 1H, J=8.45Hz, J=5. 15Hz), 4.06 (dd, 1H, J=14.85Hz, J-5. 15Hz), 3.79-3.89 (m, 4H), 3.71 (s, 3H), 3.53-3.61 (m, 2H), 3.18 (m, 1H), 2.87 (m, 1H) Example 12 Synthesis of 1- [N- (5, 6-dimethyl-2-methoxypyridin-3-yl) aminocarbonyl]-4- diphenylmethylene-piperidine N- (5, 6-dimethyl-2-methoxypyridin-3-yl) phenylcarbamate (50mg, 0. 184 mmol) and 4-diphenylmethylene-piperidine HCl (52.5mg, 0.184mmol) were mixed in anhydrous THF (5m2), and then DBU (60.7, d, 0.41mmol) was added dropwise to this reaction solution.

After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50mEx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and hexane to give 44.7mg (Yield 51.3%) of the title compound as a solid.

m. p.: 190-192 °C 'H NMR (300MHz, CDCl3) : 6 ppm 8.16 (s, IM, 7.11-7.32 (m, lOH), 6.86 (br, 1H), 3.93 (s, 3H), 3.55 (t, 4H, J=5.67Hz), 2.46 (t, 4H, J=5.67Hz), 2.32 (s, 3H), 2.17 (s, 3H) Example 13 Synthesis of 1-[N-(diphenylmethyl) aminocarbonyl]-4-diphenylmethylene- piperidine N- (diphenylmethyl) phenylcarbamate (100mg, 0. 33mmol) and 4-diphenylmethyl- ene-piperidine HCl (94.2mg, 0.33mmol) were mixed in anhydrous THF (5m#), and then DBU (108/, 0.72mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with methylene chloride (50m#x3).

The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and diethylether to give 100.7mg (Yield 66. 5%) of the title compound as a solid. m. p.: 206°C 'HNMR (300MHz, CDC13) : 6 ppm 7.09-7.34 (m, 20H), 6.16 (d, 1H, J=6.78Hz), 4.99 (d, 1H, J=6.78Hz), 3.48 (t, 4H, J=5.67Hz), 2.40 (t, 4H, J=5.67Hz) "C NMR (75MHz, CDC13) : # ppm 184.45,151.07,146.37,142.65,129.60, 128.59,128.09,127.35,127.22,126.58,58.37,45.27,31.29 Example 14 Synthesis of 1-[N-(2, 2-diphenylethan-1-yl) aminocarbonyl]-4-diphenylmethyl- ene-piperidine N- (2, 2-diphenylethan-1-yl) phenylcarbamate (500mg, 1.57mmol) and 4-diphenyl methylene-piperidine-HCl (450mg, 1.57mmol) were mixed in anhydrous THF (5mut), and

then DBU (0. 5mua, 3.31mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with methylene chloride (soma x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and diethylether to give 519.4mg (Yield 70.0%) of the title compound as a solid. m. p.: 158-160°C IH NMR (300MHz, CDCl3) : 6 ppm 7.06-7.32 (m, 20H), 4.42 (t, 1H, J=5.69Hz), 4.23 (t, 1H, J=7.86Hz), 3.86 (dd, 2H, J=5.69Hz, J=7.86Hz), 3.25 (dd, 4H, J=5.70 Hz, J=5.85Hz), 2.27 (dd, 4H, J=5.67, J=5. 85Hz) "C NMR (75MHz, CDCl3) : 6 ppm 157.22.142.12,141,93,137.37,133.69, 129.54,128.58,128.07,128.01,126.63,126.49,50.85,45.22,44.91, 31.08 Example 15 Synthesis of 1- [N- (5, 6-dimethyl-2-methoxypyridin-3-yl) aminocarbonyl]-4, 4- diphenyl-piperidine N- (5, 6-dimethyl-2-methoxypyridin-3-yl) phenylcarbamate (60mg, 0.25mmol) and 4,4-diphenylpiperidine (60mg, 0.25mmol) were mixed in anhydrous THE (lOmQ), and then DBU (48, aR, 0.32mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 56mg (Yield 54%) of the title compound as a syrup.

'H NMR (300MHz, CDCl3) : 6 ppm 8.11 (s, 1H), 7.17,6.84 (2m, 10H), 6.40 (br, 1H), 3.96 (s, 3H), 4.24,3.57,2.72,2.48,1.90,1.74 (m, 8H), 2.33,2.16 (s, 6H) Example 16

Synthesis of l-[N-(2-methoxyquinoxalin-3-yl) aminocarbonyl]-4, 4-diphenyl- piperidine N-(2-methoxyquinoxalin-3-yl) phenylcarbamate (73.8mg, 0.25mmol) and 4,4- diphenylpiperidine (60mg, 0.25mmol) were mixed in anhydrous THE (lOmQ), and then DBU (48, at, 0. 32mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and hexane to give 72mg (Yield 65.7%) of the title compound as a solid. m. p.: 202-204°C 'H NMR (300MHz, CDC13) : 6 ppm 14.37 (br, 1H), 7.79-7.19 (m, 14H), 4.14 (s, 3H), 4. 21,3.68,2.57,1.93,1.62 (5m, 8H) Example 17 Synthesis of l-[N-(diphenylmethyl) aminocarbonyl]-4, 4-diphenyl-piperidine N- (diphenylmethyl) phenylcarbamate (96mg, 0.32mmol) and 4,4-diphenylpiperidine (76mg, 0.32mmol) were mixed in anhydrous THE (lOmQ), and then DBU (64td, 0.43mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50mx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate to give 94mg (Yield 65.8%) of the title compound as a solid. m. p.: 232-234°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.24 (m, lOH), 6.12 (d, 1H), 4.95 (d, 1H, J=6. 42Hz), 3.47,2.42 (2m, 8H)

Example 18 Synthesis of l-[N-(diphenylmethyl) aminocarbonyl]-4-hydroxycarbonyl-4- phenyl-piperidine N- (diphenylmethyl) phenylcarbamate (100mg, 0.33mmol) and 4-hydroxycarbonyl- 4-phenyl-piperidine (124.5mg, 0.33mmol) were mixed in anhydrous TE (lOmQ), and then DBU (49, u. e, 0.33mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with methylene chloride (50mA) and water of pH 4 (50mu). The aqueous layer was adjusted to pH 7 and crystallized to give 81. 5mg (Yield 59.6%) of the title compound as a solid. m. p.: 208°C 'H NE (300MHz, CDC13) : 8 ppm 7.22-7.42 (m, 15H), 6.09 (d, 1H, J=8.61Hz), 3.98 (d, 2H, J=13.56Hz), 2.98 (dd, 2H, J=11.70, J=12.27Hz), 2.40 (d, 2H, J=12.81 Hz), 1.73 (dd, 2H, J=10. 44Hz, J=10. 62Hz) 13C NMR (75MHz, CDC13) : 6 ppm 175.24,156.95,143.44,142.91,128.53, 128.15,127.52,126.93,126.64,125.74,57.48,48.83,41.85,33.35 Example 19 Synthesis of 1- [N- (5-ethyl-6-methyl-2-methoxypyridin-3-yl) aminocarbonyl]-4- hydroxycarbonyl-4-phenyl-piperidine N- (5-ethyl-6-methyl-2-methoxypyridin-3-yl) phenylcarbamate (60mg, 0.21 mmol) and 4-hydroxycarbonyl-4-phenyl-piperidine (79.1mg, 0.21mmol) were mixed in anhydrous THF (6mA), and then DBU (65.80,0.44mmol) was added dropwise to this reaction solution.

After stirring for 3 hours at room temperature, the product was extracted with methylene chloride (50mut) and water of pH 4 (50mu). The aqueous layer was adjusted to pH 7 and crystallized to give 79.3mg (Yield 95.2%) of the title compound as a solid. m. p. : 173-174°C 'H NMR (300MHz, CDCl3) : 8 ppm 7.71 (s, 1H), 7.23-7.67 (m, 5H), 3.83 (s, 3H),

3.74 (d, 2H, J=13.53Hz), 3.04 (dd, 2H, J=12.09Hz, J=12.27Hz), 2.48 (q, 2H, J=7.5Hz), 2.42 (d, 2H, J=13. 02Hz), 2.31 (s, 3H), 1.78 (dd, 2H, J=10. 44Hz, J= 10. 62Hz), 1. 08 (t, 3R J=7.50Hz) "C NMR (75MHz, CDC13) : # ppm 175.16,155.09,152.85,145.89,142.78, 131.24,128.93,128.55,126.97,125.75,120.97,53.01,48.76,41.88, 33.25,24.33,20.80, 14.49 Example 20 Synthesis of 1-[N-(2, 2-diphenylethan-1-yl) aminocarbonyl]-4-hydroxy carbonyl-4-phenyl-piperidine N-(2,2-diphenylethan-1-yl)phenylcarbamate(1g, 3.15mmol) and 4-hydroxy carbonyl-4-phenyl-piperidine (1. 19g, 3.15mmol) were mixed in anhydrous THF (10m#), and then DBU(1m#, 6.62mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with methylene chloride (100 mt) and water of pH 4 (100m#). The aqueous layer was adjusted to pH 7 and crystallized to give 0.75g (Yield 55. 8%) of the title compound as a solid. m. p.: 173-174°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.01-7.31 (m, 15H), 6.50 (t, 1H, J=5.49Hz), 4.22 (t, 1H, J=7.71Hz), 3.65 (d, 2H, J=13.74Hz), 3.58 (dd, 2H, J=5.49Hz, J=7.71 Hz), 2.72 (dd, 2H, J=11.70Hz, J=11. 91Hz), 2.14 (d, 2H, J=13. 2Hz), 1.39 (dd, 2H, J=9.9Hz, J=11. 16Hz) '3C NMR (75MHz, CDC13) : 6 ppm 175.21,157.33,143.11,142.93,128.44, 128.26,128.00,126.87,126.12,125.67,50.45,48.84,44.69,41.86,3 2.91 Example 21 Synthesis of 1- [N- (5-ethyl-6-methyl-2-methoxypyridin-3-yl) aminocarbonyt] spiro [isobenzofuran-1 (3H), 4-piperidin]-3-one N- (S-ethyl-6-methyl-2-methoxypyridin-3-yl) phenylcarbamate (40mg, 0.20 mmol)

and spiro [isobenzofuran-1 (3H), 4-piperidin]-3-one (56.3mg, 0.20mmol) were mixed in anhydrous THF (lOmQ), and then DBU (35ß, 0. 22mmol) was added dropwise to this reaction solution. After stirring for 6 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent : ethyl acetate: hexane=1 : 5, v/v) to give 64mg (Yield 88.2%) of the title compound as a solid.

'H NMR (300MHz, CDCI3) : 6 ppm 8.20 (s, 1H), 7.91 (d, IM, 7.71,7.57 (t, 2H), 7.27 (d, 1H), 4.19 (m, 2H), 3.97 (s, 3H), 3.45 (m, 2H), 2. 57 (m, 2H), 2.25 (s, 3H), 2.16 (m, 2H), 1.80 (m, 2H), 1. 19 (t, 3Ep Example 22 Synthesis of 1- [N- (2-methoxyquinoxalin-3-yl) aminocarbonyl] spiro [isobenzo- furan-1 (3H), 4-piperidin]-3-one N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (26mg, 0.13mmol) and spiro [isobenzofuran-1 (3H), 4-piperidin]-3-one (37mg, 0.13mmol) were mixed in anhydrous THF (5mu), and then DBU (24, u, , 0.16mmol) was added dropwise to this reaction solution.

After stirring for 5 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 43mg (Yield 89.2%) of the title compound as a solid.

'H NMR (300MHz, CDCl3) : S ppm 7.9-7.21 (m, 8H), 5.04 (m, 2H), 4.25 (m, 2H), 4.16 (m, 2H), 4.12 (s, 3H), 3.56 (m, 2H), 2.42 (m, 2H), 2.25 (s, 3H), 2.16 (m, 2H), 1. 80 (m, 2H), 1. 19 (t, 3H) Example 23

Synthesis of 1- [ (5, 6-dimethyl-2-methoxypyridin-3-yl) aminocarbonyl]-4- (diphenylmethyl) piperazine N- (5, 6-dimethyl-2-methoxypyridin-3-yl) phenylcarbamate (54.4mg, 0.2mmol) and 1- (diphenylmethyl) piperazine (52mg, 0.2mmol) were mixed in anhydrous THF (lOmQ), and then DBU (40, ut, 0.27mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50mA x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and hexane to give 71mg (Yield 88.3%) of the title compound as a solid. m. p.: 132-134°C 'HNMR (300MHz, CDCtg) : 6 ppm 8.14 (s, 1H), 7.43,7.29,7.19 (3m, lot), 4. 25 (s, 1H), 3.91 (s, 3H), 3.49 (m, 4H), 2.44 (m, 4H), 2.16 (s, 3H), 2.04 (s, 3H) Example 24 Synthesis of 1- [ (5, 6-dimethyl-2-methoxypyridin-3-yl) amino-N-cyanocarbo- imidate]-4- (3, 5-dimethylphenyl) piperazine 1- (3, 5-Dimethylphenyl) piperazine (400mg, 2. lmmol) and diphenyl-N-cyano carboimidate (550.9mg, 2.3mmol) were mixed in anhydrous DMF (lOmQ), and then 60% NaH (92.5mg, 2.3mmol) was added dropwise to this reaction solution. After stirring for 30 minutes at room temperature, the product was extracted with ethyl acetate (100aux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and diethylether to give 523mg (Yield 67.9%) of the intermediate compound 1- (phenoxy-N-cyanocarboimidate)-4- (3, 5-dimethylphenyl) piperazine as a solid. The intermediate l7. 8mg, 0.32mmol) thus obtained and 5,6- dimethyl-2-methoxy-3-amino-pyridine (48. 9mg, 0.32mmol) were mixed in anhydrous

THF (lOmQ), and then 60% NaH (34mg, 0.85mmol) was added dropwise to this reaction solution. After stirring for 24 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 62.8mg (Yield 50%) of the title compound as a solid. m. p.: 214-217°C IHNMR (300M : Hz, CDC13) : 6 ppm 7.19 (s, 1H), 6.73 (s, 1H), 6.57 (s, 1H), 6.52 (s, 2H), 4.20 (s, 3H), 3.58 (t, 4H, J=5.13Hz), 3.14 (t, 4H, J=5. 13Hz), 2.36 (s, 3H), 2.27 (s, 6H), 2.18 (s, 3H) Example 25 Synthesis of 1- [ (5, 6-dimethyl-2-methoxypyridin-3-yl) aminocarbonyl]-4- [4, 6- bis (propylamino)-1, 3,5-triazin-2-yl] piperazine N- (5, 6-dimethyl-2-methoxypyridin-3-yl) phenylcarbamate (60mg, 0.22mmol) and 1- [4, 6-bis (propylamino)-1, 3,5-triazin-2-yl] piperazine (74.3mg, 0.27mmol) were mixed in anhydrous THF (10m#), and then DBU (40.4,0. 27mmol) was added dropwise to this reaction solution. After stirring for 30 minutes at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=l : 1, v/v) to give 102mg (Yield 98%) of the title compound as a solid. m. p.: 140-143°C 1H NMR(300MHz, CDCl3) : 6 ppm 8.13 (s, lEp, 6.84 (s, 1H), 4.25 (s, 2H), 3.97 (s, 3H), 3.72 (s, 4H), 3. 55 (s, 4H), 3.37 (s, 2H), 2. 33 (s, 3H), 2.18 (s, 3H), 1.63 (m, 2H), 1.46 (m, 2H), 0.97 (t, 3H), 0.93 (t, 3H)

Example 26 Synthesis of 1-[(2-methoxy-5-cyanophenyl) aminocarbonyl]-4-(3, 5-dimethyl phenyl) piperazine N- (2-methoxy-5-cyanophenyl) phenylcarbamate (500mg, 1.73mmol) and 1- (3, 5- dimethylphenyl) piperazine (330mg, 1. 73mmol) were mixed in anhydrous THF (lOmQ), and then DBU (0.26mA, 1.73mmol) was added dropwise to this reaction solution. After stirring for 24 hours at room temperature, the product was extracted with ethyl acetate (100aux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=l : l, v/v) to give 483mg (Yield 98%) of the title compound as a solid.

IHN (300MHz, CDC13) : 8 ppm 9.09 (s, 1H), 7.89 (d, 1H, J=8.97Hz), 7.17 (s, 1H), 6.89 (d, 1H, J=8.97Hz), 6.57 (s, 3H), 4.00 (s, 3H), 3.67 (d, 4X J=3.66Hz), 3.23 (d, 4H, J=3.84Hz), 2.29 (s, 6H) Example 27 Synthesis of 1- [ (1, 4-benzodioxan-6-yl) amino-N-cyanocarboimidate]-4- (3, 5- dimethylphenyl) piperazine (1, 4-Benzodioxan-6-yl) amine (450mg, 3mmol) and diphenyl-N-cyano carboimidate (857mg, 3.2mmol) were mixed in anhydrous DMF (10m#), the resulting solution was cooled to 0 °C, and then NaH (86.4mg, 3.2mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (lOOmEx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Without purification, the intermediate compound, N- (1, 4-benzodioxan-6-yl) aminophenyl-N-cyanocarboimidate (295mg, l. 00mmol) and 1- (3, 5- dimethylphenyl) piperazine (209mg, 1. 2mmol) were mixed in anhydrous DMF (3m) and

then NaH (26mg, 0.85mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from petrolium ether and methylene chloride to give 157mg (Yield 40%) of the title compound as a solid. m. p.: 201-203°C IH NMR (300MHz, CDCl3) : 6 ppm 10.66 (s, 1H), 6.62 (s, 2H), 6.54 (s, 1H), 6.50 (s, 2H), 4.24 (s, 4H), 3.51 (t, 4H, J=5. 03Hz), 3.09 (t, 4H, J=5.03Hz), 2.26 (s, 6H) Example 28 Synthesis of 1-[(benzo-1, 2,4-triazin-1-N-oxide-3-yl) aminocarbonyl]-4- (3,5- dimethylphenyl) piperazine 3-Amino-benzo-1,2,4-triazin-1-N-oxide (45mg, 0.3mmol), 1- (3, 5-dimethylphenyl) piperazine (57mg, 0.3mmol), and 1, 1'-carbonyldiimidazole (81mg, 0. 5mmol) were mixed in anhydrous THF (20m#), and then DBU (112, zQ, 0. 7mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (50mex3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=l : 1, v/v) to give 75mg (Yield 68.7%) of the title compound as a solid.

'H NMR (300MHz, CDC13) : 6 ppm 7.90,7.23,7.11,6.56 (4m, 7H, Ph), 3.75 (m, 4H), 3.22 (m, 4H), 2.27 (s, 6H) Example 29 Synthesis of 1-[(benzo-1, 2,4-triazin-l-N-oxide-3-yl) aminocarbonyl]-4-diphenyl methyl) piperazine

3-Amino-benzo-1,2,4-triazin-1-N-oxide (30mg, 0.2mmol), 1- (diphenylmethyl) piperazine (52mg, 0.2mmol), and 1, 1'-carbonyldiimidazole (49mg, 0.32mmol) were mixed in anhydrous THF (lOmt), and then DBU (480, 0. 32mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (50maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 43mg (Yield 50.4%) of the title compound as a syrup.

'H NE (300MHz, CDC13) : 6 ppm 7.83-7.05 (m, 14H), 4.28 (s, 1H), 3.61,2.46 (2m, 8H) Example 30 Synthesis of 1-[(2-phenylvinyl) aminocarbonyl]-4-(3, 5-dimethylphenyl) piperazine (2-Phenylvinyl) amine (59.5mg, 0. 5mmol), 1- (3,5-dimethylphenyl) piperazine (105 mg, 0. 5mmol), and 1, 1'-carbonyldiimidazole (81mg, 0. 5mmol) were mixed in anhydrous THF (20mA), and then DBU (288, uQ, 1. 8mmol) was added dropwise to this reaction solution.

After stirring for 6 hours at room temperature, the product was extracted with ethyl acetate (50aux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 110. 8mg (Yield 66.5%) of the title compound as a syrup.

'H NMR (300MHz, CDCl3) : 8 ppm 7.70 (d, J=15.29Hz, 1H), 7.24-7.55 (m, 5H), 6.91 (d, J=15.39Hz, 1H), 6.57 (m, 3H), 3.81,3.19 (t, J=5.31Hz, 8H), 2.28 (s, 6H) Example 31 Synthesis of 1-[(diphenylmethyl) aminocarbonyl]-4-(diphenylmethyl)

piperazine N- (diphenylmethyl) phenylcarbamate (121.2mg, 0.4mmol) and 1- (diphenylmethyl) piperazine (104mg, 0.4mmol) were mixed in anhydrous THF (lOmQ), and then DBU (80, uQ, 0. 53mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50mA x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was washed with methylene chloride to give 136mg (Yield 73.6%) of the title compound as a solid. m. p.: 216-218°C IH NMR (300MHz, CDCl3) : 8 ppm 7.40,7.23 (2m, 20H), 6.02 (d, 1H, J=8.4 Hz), 4.30 (s, 1H), 3.37 (m, 4H), 2.24 (m, 4H) Example 32 Synthesis of 1-[(diphenylmethyl) aminocarbonyl]-4-(3, 5-dimethylphenyl) piperazine N- (diphenylmethyl) phenylcarbamate (50mg, 0.16mmol) and 1- (3, 5-dimethyl phenyl) piperazine (31. 4mg, 0.16mmol) were mixed in anhydrous THF (lord) and then DBU (54, LDQ, 0.36mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50mtx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate to give 37. 4mg (Yield 56.8%) of the title compound as a solid. m. p.: 173-174 °C 'H NMR (300MHz, CDC13) : 8 ppm 7.23-7.35 (m, 10H), 6.54 (s, 3H), 6.16 (d, 1H, J=6.78Hz), 5.05 (d, 1H, J=6.78Hz), 3.55 (t, 4H, J=5.31Hz), 3.15 (t, 4H, J=5. 31Hz),

2.27 (s, 6H) Example 33 Synthesis of l-[(diphenylmethyl) aminothiocarbonyl]-4-(diphenylmethyl) piperazine Aminodiphenylmethane (500mg, 2.7mmol), 1- (diphenylmethyl) piperazine (486mg, 2.7mmol), and 1, 1'-thiocarbonyldiimidazole (486mg, 2.7mmol) were mixed in anhydrous THF (10m#), and then DBU (8200, 5. 5mmol) was added dropwise to this reaction solution.

After stirring for 19 hours at room temperature, the product was extracted with ethyl acetate (50mEx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 20, v/v) to give 144mg (Yield 11.5%) of the title compound. m. p.: 118-120°C tHNMR (300MElz, CDC13) : 6 ppm 7.15-7.41 (m, 20H), 6.94 (d, IH, J=7.41Hz), 5.90 (d, 1H, J=7. 41Hz), 4.24 (s, 1H), 3.82 (t, 4H, J=5. 1Hz), 2.45 (t, 4H, J=5. 1Hz) Example 34 Synthesis of 1- [ (diphenylmethyl) aminocarbonyl]-4- [4, 6-bis (propylamino)- 1,3,5-triazin-2-yl] piperazine N- (diphenylmethyl) phenylcarbamate (29.6mg, 0.098mmol) and 1- [4, 6-bis (propyl amino)-1, 3,5-triazin-2-yl] piperazine (10. 5mg, 0.098mmol) were mixed in anhydrous THF (lmB), and then DBU (14.6, u, , 0.098mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (50mx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl

acetate: hexane=1 : 4, v/v) to give 9.6mg (Yield 52.3%) of the title compound as a syrup.

'H NMR (300MHz, CDCl3) : 6 ppm 7.19-7.35 (m, 10H, 6.16 (d, 1H, J=6.69Hz), 5.01 (d, 1H, J=6.69Hz), 4.24 (s, 2H), 3.84 (s, 4H), 3.45 (s, 4H), 3.34 (s, 2H), 1.58 (m, 2H), 1.44 (m, 2H), 0.94 (t, 3H, J=7.24Hz), 0.94 (t, 3H, J=7.23 Hz) Example 35 Synthesis of 1-[(diphenylmethy1) amino-N-cyanocarboimidate]-4-(3, 5- dimethylphenyl) piperazine Aminodiphenylmethane (0. 56m#, 3.27mmol) and diphenyl-N-cyanocarboimidate (936mg, 3.93mmol) were mixed in anhydrous DMF (12me), and then TEA (0. 55mi, 3.93mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (100mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and diethylether to give 1.045g (Yield 97.6%) of the intermediate compound N- (diphenylmethyl) amino-phenoxy-N-cyanocarboimidate as a solid. The intermediate (200mg, 0.61mmol) thus obtained and 1- (3, 5- dimethylphenyl) piperazine (116. 2mg, 0.61mmol) were mixed in anhydrous DMF (3mA), and then 60% NaH (24.4mg, 0.61mmol) was added dropwise to this reaction solution. After stirring for 1 hour at 80 C, the product was extracted with ethyl acetate (50m. ex3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 1, v/v) to give 152.1mg (Yield 58.6%) of the title compound. m. p.: 205-208°C 'H NMR (300MHz, CDC13) : 6 ppm 7.23-7.34 (m, lOH), 6.56 (s, 1H), 6.50 (s, 2H), 6.24 (d, 1H, J=8.03Hz), 5.96 (d, 1H, J=8.03Hz), 3.62 (t, 4H), 3.14 (t, 4H,), 2.26 (s, 6H) 13C NMR (75M : Hz, CDCl3) : # ppm 160.10,150.65,140.79,138.84,128.82,

127.85,127.43,122.56,117.29,114.49,61.11,49.21,46.96,21.61 Example 36 Synthesis of 1-[(2, 2-diphenylethan-1-yl) aminocarbonyl]-4-(3, 5-dimethyl phenyl) piperazine N- (2, 2-diphenylethan-1-yl) phenylcarbamate (50mg, 0.16mmol) and 1- (3, 5- dimethylphenyl) piperazine (30. 0mg, 0. 16mmol) were mixed in anhydrous THF (5A) and then DBU (260, 0.17mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from hexane to give 43.2mg (Yield 66.2%) of the title compound as a solid. m. p.: 174-175°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.19-7.33 (m, 10H), 6.51 (s, 3H), 4.41 (br, 1H), 4.26 (t, 1H, t=7.7Hz), 3.88 (dd, 2H, J=5.7,7.7Hz), 3.35 (t, 4H, J=4.77 Hz), 3.05 (t, 4H, J=4.77Hz), 2.26 (s, 6H) "C NMR (75MHz, CDCl3) : S ppm 157.38,151.08,142.10,138.72,128.66, 128.12,126.73,122.21,114.42,50.86,49.19,45.22,43.67,21.57 Example 37 Synthesis of 1-[(2, 2-diphenylethan-1-yl) aminocarbonyl]-4-(diphenylmethyl) piperazine N- (2, 2-diphenylethan-1-yl) phenylcarbamate (50mg, 0.16mmol) and 1- (diphenyl methyl) piperazine (39.8mg, 0.16mmol) were mixed in anhydrous THF (5me), and then DBU (260, 0.17mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50nAx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over

anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=3: 7, v/v) to give 63.1mg (Yield 89.2%) of the title compound as a solid. m. p.: 175-176°C 'HNMR (300MHz, CDCI3) : 8 ppm 7.13-7.38 (m, 20H), 4.34 (br, IH), 4.20 (t, 1H, t=7.7Hz), 4.16 (s, 1H), 3.83 (dd, 2H, J=5.9,7.7Hz), 3.18 (t, 4H, J=4.92Hz), 2.27 (t, 4H, J=4.92Hz) '3C NMR (75MHz, CDCl3) : # ppm 157.52,142.33,142.18,128.67,128.59, 128.15,127.85,127.10,126.72,76.01,51.46,50.89,45.18,43.82 Example 38 Synthesis of 1- [ (diphenylmethyl) aminocarbonyl]-4- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine N- (diphenylmethyl) phenylcarbamate (70mg, 0.23mmol) and 1- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine (63.5mg, 0.23mmol) were mixed in anhydrous THF (4mg), and then DBU (34.5flt, 0.23mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (SOmEx3).

The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 77.4mg (Yield 69.4%) of the title compound as a solid. m. p.: 182-184°C 'H NMR (300MHz, CDC13) : 6 ppm 7.25-7.32 (m, 10H), 6.16 (d, 1H, J=4.58Hz), 5.89 (m, 2H), 5.19 (d, 2H), 5.09 (d, 2H), 5.04 (d, 1H, J=4.58Hz), 3.99 (s, 4H), 3.78 (s, 4H), 3.43 (s, 4EI) 13C NMR (75MHz, CDCl3) : 6 ppm 165.06,156. 70,142.40,135.19,128.59, 127. 34,127.27,115.62,58.36,43.62,43.15,42.62,29.65 EI MS, m/e = 484

Example 39 Synthesis of 1-[(diphenylmethyl) aminocarbonyl]-4-14, 6-bis-(allyl- cyclohexyl-amino)- [1, 3,5] triazin-2-yl] piperazine N- (diphenylmethyl) phenylcarbamate (35.1mg, 0.12mmol) and 1- [4, 6-bis- (allyl- cyclohexyl-amino)-[1, 3, 5]triazin-2-yl]piperazine (50.8mg, 0. 12mmol) were mixed in anhydrous THF (4m#), and then DBU (17.3, uQ, 0.12mmol) was added dropwise to this reaction solution. After stirring for 15 hours at room temperature, the product was extracted with ethyl acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 61. 0mg (Yield 81. 3%) of the title compound as a solid. m. p.: 200-202°C 'H NMR (300MHz, CDCl3) : S ppm 7.25-7.35 (m, lOH), 6.17 (d, 1H, J=6. 6Hz), 5.83-5.92 (m, 2H), 5.11 (d, 2H), 5.00 (d, 2H), 4.96 (d, 1H, J=6.6Hz), 4.43 (br, 2H), 4.21 (d, 4H), 3.77 (s, 4H), 3.44 (s, 4H), 1.12-1.77 (m, 20H) Example 40 Synthesis of l-[(diphenylmethyl) aminocarbonyl]-4-44, 6-bis-[ethyl-(2-methyl allyl) amino]- [1, 3,51triazin-2-yl} piperazine N- (diphenylmethyl) phenylcarbamate (50.9mg, 0.17mmol) and 1-t4, 6-bis-[ethyl- (2-methylallyl) amino]- [1, 3,5] triazin-2-yl} piperazine (60.3mg, 0.17mmol) were mixed in anhydrous THF (4mut), and then DBU (25. 1µ#, 0.17mmol) was added dropwise to this reaction solution. After stirring for 15.5 hours at room temperature, the product was extracted with ethyl acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and

concentrated under reduced pressure. The residue was separated by column chromatography (eluent : ethyl acetate: hexane=1 : 4, v/v) to give 86.5mg (Yield 90.7%) of the title compound as a solid. m. p.: 178-180°C 'H NMR (300MHz, CDCl3) : 8 ppm 7.19-7.35 (m, 10H), 6.16 (d, 1H, J=6. 48Hz), 5.00 (d, 1H, J=6.48Hz), 4.79 (d, 4H), 4.12 (s, 4H), 3.79 (s, 4H), 3.45 (s, 8H), 1.67 (s, 6H), 1. ll (s, 6H) Example 41 Synthesis of 1- [ (diphenylmethyl) aminocarbonyll-4- (4, 6-bis-diallylamino- [1, 3, 5]triazin-2-yl)piperazine N- (diphenylmethyl) phenylcarbamate (75.7mg, 0.25mmol) and 1- (4, 6-bis-diallyl amino- [1, 3,5] triazin-2-yl) piperazine (88.7mg, 0.25mmol) were mixed in anhydrous THF (4 m#), and then DBU (37. 3 µ#, 0.25mmol) was added dropwise to this reaction solution. After stirring for 19 hours at room temperature, the product was extracted with ethyl acetate (50 m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 116.4mg (Yield 82.5%) of the title compound as a solid. m. p.: 158-159°C 'H NMR (300MHz, CDC13) : # ppm 7.16-7.35 (m, 10H), 6.16 (d, 1H, J=6. 78Hz), 5.75-5.88 (m, 4H), 5.12 (dd, 4H), 5.07 (dd, 4H), 4.98 (d, 1H), 4.12 (d, 8EI), 3.78 (t, 4H), 3.42 (t, 4H) Example 42 Synthesis of l-[(diphenylmethyl) aminocarbonyl]-4-(4, 6-bis-cyclopropylmethyl amino- [1, 3,5] triazin-2-yl) piperazine

N- (diphenylmethyl) phenylcarbamate (51.6mg, 0.17mmol) and 1- (4, 6-bis-cyclo propylmethylamino- [1, 3,5] triazin-2-yl) piperazine (51. 6mg, 0.17mmol) were mixed in anhydrous THF (4mQ), and then DBU (25. 4µ#, 0.17mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (some3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=l : 1, v/v) to give 82.7mg (Yield 94.9%) of the title compound as a solid. m. p.: 186-188°C 'HNMR (300MHz, CDCl3) : 6 ppm 7. 25-7.35 (m, lot), 6.17 (d, 1H), 4.99 (d, 1H), 4.92 (s, 2H), 3.79 (s, 4H), 3.44 (dd, 4H), 3.21 (t, 4H), 0.99-1.05 (m, 2H), 0.30 (dt, 4H), 0.21 (dt, 4H) Example 43 Synthesis of 1-[(2, 2-diphenylethan-1-yl) amino-N-cyanocarboimidate]-4-(4, 6- bis-allylamino- [1, 3,5] triazin-2-yl) piperazine N- (2, 2-diphenylethan-1-yl) amino-phenoxy-N-cyanocarboimidate (155mg, 0.45 mmol) and 1- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine (125mg, 0.45mmol) were mixed in DMF (5mut), and then 60% NaH (18.2mg, 0.45mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=9 : 1, v/v) to give 65.9mg (Yield 27.8%) of the title compound as a solid. m. p.: 117-120°C 'H NMR (300MHz, CDC13) : 6 ppm 7.26-7.37 (m, lOH), 5.85-5.94 (m, 2H),

5.20 (dd, 2H, J=17.22Hz, J=1.47Hz), 5.11 (dd, 2H, J=10.26Hz, J=1.47Hz), 4.90 (br, 2H, NH), 4.64 (t, 1H, J=5. 28Hz), 4.30 (t, 1H, J=8.04Hz), 4.09 (dd, 2H, J=8.04Hz, J=5. 28Hz), 3.98 (t, 4H), 3.69 (s, 4H), 3.26 (t, 4H) Example 44 Synthesis of l-[(diphenylmethyl) amino-N-cyanocarboimidate]-4-(4, 6-bis- allylamino- [1,3,5] triazin-2-yl) piperazine N- (diphenylmethyl) amino-phenoxy-N-cyanocarboimidate (142.8mg, 0.44mmol) and 1- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine (120.1mg, 0.44mmol) were mixed in anhydrous DMF (5m4), and then 60% NaH (17. 4mg, 0.44mmol) was added dropwise to this reaction solution. After stirring for 6 hours at 80 °C, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2: 1, v/v) to give 135.7mg (Yield 61.2%) of the title compound as a solid. m. p.: 116-118°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.24-7.34 (m, lOH), 6.22 (d, 1H, J=7.59Hz), 5.83-5.93 (m, 2H), 5.77 (d, 1H, J=7.59Hz), 5.18 (dd, 2H, J=17. 04Hz, J=1.47Hz), 5.09 (dd, 2H, J=10. 05Hz, J=1. 47Hz), 5.07 (s, 2H), 3.97 (s, 4H), 3.78 (s, 4H), 3.50 (s, 4H) Example 45 Synthesis of 1-[(2, 2-diphenylethan-1-yl) aminocarbonyl]-4-(4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine N- (2, 2-diphenylethan-1-yl) phenylcarbamate (66.1mg, 0.22mmol) and 1- (4, 6-bis- allylamino- [1, 3,5] triazin-2-yl) piperazine (60mg, 0. 22mmol) were mixed in anhydrous THF (4mu), and then DBU (32.6fla, 0.22mmol) was added dropwise to this reaction solution.

After stirring for 19 hours at room temperature, the product was extracted with ethyl

acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 1, v/v) to give 81.8mg (Yield 77.5%) of the title compound as a solid. m. p.: 90-92°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.20-7.34 (m, lOH), 5.82-5.95 (m, 2H), 5.19 (dd, 2H), 5.09 (dd, 2H), 5.07 (br, 2H, NH), 4.41 (t, 1H, J=5. 51Hz), 4.23 (t, 1H, J=7.86Hz), 3.98 (t, 4H, J=5.31Hz), 3.88 (dd, 1H, J=7.86Hz, J=5. 51Hz), 3.68 (s, 4H), 3.23 (t, 4H, J=5. 31Hz) Example 46 Synthesis of 1- [5-ethyl-6-methyl-2-methoxypyridin-3-yl) aminocarbonyl]-4- (4,6-bis-allylamino- 1,3,5] triazin-2-yl) piperazine N- (5-ethyl-6-methyl-2-methoxypyridin-3-yl) phenylcarbamate (50mg, 0.17mmol) and 1- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine (48.1mg, 0.17mmol) were mixed in anhydrous THF (4mt), and then DBU (26.1SQ, 0.17mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (50maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 2, v/v) to give 27mg (Yield 34%) of the title compound as a solid. m. p.: 136-137 C 'H NMR (300MHz, CDC13) : 6 ppm 8.19 (s, 1H), 6.88 (s, 1H), 5.90 (m, 2H), 5.22 (dd, 2H), 5.12 (dd, 2H), 4.02 (t, 4ES), 3.97 (s, 3H), 3.86 (s, 4H), 3. 54 (t, 4H), 2.52 (q, 2H, J=0. 5Hz), 2.37 (s, 3H), 1.17 (t, 3H, J=0, 5Hz) 13C NMR (75MHz, CDC13) : # ppm 164.99,154.68,150.13,144.81,135.10, 130.05,126.50,121.07,115.74,53.41,43.62,43.19,42.68,29.67,25 .26,20.85,14.57

Example 47 Synthesis of 1- [ (5-ethyl-6-methyl-2-methoxypyridin-3-yl) aminocarbonyl]-4- [(2, 6-dipyrrolidin-1-yl) pyrimidin-4-yl] piperazine N- (5-ethyl-6-methyl-2-methoxypyridin-3-yl) phenylcarbamate (44.3mg, 0. 15mmol) and 1-[(2, 6-dipyrrolidin-1-yl) pyrimidin-4-yllpiperazine (46.9mg, 0. 15mmol) were mixed in anhydrous THF (4mu), and then DBU (23, me, 0.15mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent : ethyl acetate: hexane=1 : 2, v/v) to give 10.2mg (Yield 13.7%) of the title compound as a solid. m.p. : 162-166 °C 'H NMR (300MHz, CDCl3) : # ppm 8.20 (s, 1H), 6.89 (s, 1H), 4.86 (s, 1H), 3.97 (s, 3H), 3.43-3.66 (m, 16H), 2.55 (q, 2H, J=7.5Hz), 2.33 (s, 3H), 1. 91 (dd, 8H, J=6.42Hz, J=2. 37Hz), 1.17 (t, 3H, J=7.5Hz) Example 48 Synthesis of 1- [N- (2-methoxyquinoxalin-3-yl) aminocarbonyl]-4- (diphenyl methyl) piperazine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (SOmg, 0.17mmol) and 1- (diphenylmethyl) piperazine (42.7mg, 0.17mmol) were mixed in anhydrous THF (5mut), and then DBU (28ß, O. l9mmol) was added dropwise to this reaction solution. After stirring for 1 hour at room temperature, the product was extracted with methylene chloride (50m# x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate and diethylether to give 43.1 mg (Yield 56.2%) of the title compound as a solid.

'H NMR (300MHz, CDCL3) : 6 ppm 14.33 (s, 1H), 7.19-7.84 (m, 4H), 4.10 (s, 3H), 4.07 (s, 1H), 3.64 (d, 4H, J=18. 84Hz), 2.46 (d, 4H, J=18. 84Hz) Example 49 Synthesis of 1-[N-(2-ethoxyquinoxalin-3-yl) aminocarbonyl]-4-(diphenyl methyl) piperazine N- (2-ethoxyquinoxalin-3-yl) phenylcarbamate (100mg, 0.32mmol) and 1- (diphenyl methyl) piperazine (80.7mg, 0.32mmol) were mixed in anhydrous THF (2mut), and then DBU (70pt, 0.45mmol) was added dropwise to this reaction solution. After stirring for 3.5 hours at room temperature, the product. was extracted with methylene chloride (30m#x3).

The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane: methylene chloride: methanol=100 : 150 : 100: 2.5, v/v) to give 73.6mg (Yield 49.3%) of the title compound as a solid. m. p.: 156-158°C 'H NMR (500MHz, CDCL3) : 6 ppm 7.19-7.79 (m, 15H), 4.58 (q, 2H), 4.31 (s, 1H), 3.61 (m, 4H), 2.50 (m, 4H), 1.46 (t, 3H) Example 50 Synthesis of 1-[N-(2-phenoxyquinoxalin-3-yl) aminocarbonyl]-4-(diphenyl methyl) piperazine N- (2-phenoxyquinoxalin-3-yl) phenylcarbamate (50mg, 0.14mmol) and 1- (diphenyl methyl) piperazine (35.3mg, 0.14mmol) were mixed in anhydrous THF (0. 7mut), and then DBU (30/C, 0. 19mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with methylene chloride (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried

over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane: methylene chloride: methanol=20: 30 : 20: 0. 5, v/v) to give 52.1mg (Yield 72.4%) of the title compound as a solid. m. p.: 208-210°C 'H NMR (500MHz, CDCL3) : 8 ppm 7.19-7.84 (m, 20H), 4.32 (s, 1H), 4.00 (s, 1H), 3.66 (m, 4H), 2.52 (m, 4H) Example 51 Synthesis of 1- [N- (2-methoxyquinoxalin-3-yl) aminocarbonyl]-4- (4, 6-bis-allyl amino- [1, 3,5] triazin-2-yl) piperazine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (80mg, 0.27mmol) and 1- (4, 6-bis- allylamino-E1, 3,5] triazin-2-yl) piperazine (74.6mg, 0.27mmol) were mixed in anhydrous THF (3mA), and then DBU (40. 5µ#, 0.27mmol) was added dropwise to this reaction solution.

After stirring for 3.5 hours at room temperature, the product was extracted with ethyl acetate (30m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=4: 1, v/v) to give 91.4mg (Yield 71.7%) of the title compound as a solid. m. p.: 158-159°C 'H NMR (500MHz, CDCL3) : 6 ppm 7.21-7.82 (m, 4H), 5.91 (m, 2H), 5.21 (d, 2H), 5.11 (d, 2H), 4.93 (s, 2H, NH), 4.15 (d, 3H), 3.83-4.01 (m, 8H), 3.65 (t, 4H) Example 52 Synthesis of l-[N-(2-methoxyquinoxalin-3-yl) aminocarbonyl]-4-{4, 6-bis-[ethyl - (2-methylallyl) amino]- [1, 3,5] triazin-2-yl} piperazine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (79.2mg, 0.27mmol) and 1- {4, 6-

bis- [ethyl- (2-methylallyl) amino]- [1, 3,5] triazin-2-yl} piperazine (96.4mg, 0.27mmol) were mixed in anhydrous THF (3mu), and then DBU (40.1, aQ, 0.27mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (30m. ex3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate : hexane=1 : 4, v/v) to give 63.8mg (Yield 42.2%) of the title compound as a solid. m. p.: 150-152°C 'H NMR (500MHz, CDCL3) : 6 ppm 7.49-7.84 (m, 4H), 4.80 (s, 4H), 4.15 (s, 3H), 4.15 (s, 4H), 3.91 (m, 4H), 3.63 (s, 4H), 3.50 (s, 4H), 1.69 (s, 6H), 1.12 (t, 6H) Example 53 Synthesis of 1- [N- (2-methoxyquinoxalin-3-yl) aminocarbonyl]-4- (4, 6-bis- diallylamino- [1, 3,5] triazin-2-yl) piperazine N- (2-methoxyquinoxalin-3-yl) phenylcarbamate (84.5mg, 0.29mmol) and 1- (4, 6- bis-diallylamino- [1, 3,5] triazin-2-yl) piperazine (101. 7mg, 0.29mmol) were mixed in anhydrous THF (4mt), and then DBU (42. 8µ#, 0.29mmol) was added dropwise to this reaction solution. After stirring for 3.5 hours at room temperature, the product was extracted with ethyl acetate (50m#X3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 4, v/v) to give 111. 7mg (Yield 69.2%) of the title compound as a solid. m. p.: 143-145°C 'H NMR (50OMHz, CDCL3) : 8 ppm 7.69 (br, 2H), 7.42 (br, 2H), 5.80-5.83 (m, 4H), 5.12 (d, 4H), 5.10 (d, 4H), 4. 14 (m, 11H), 3.87 (s, 4H), 3.66 (s, 4H)

Example 54 Synthesis of 1-[(5-fluoro-1H-pyrimidin-2,4-dioxo-1-yl)carbonyl]-4-(3, 5- dimethylphenyl) piperazine N- (5-fluoro-lH-pyrimidin-2, 4-dioxo-1-yl) phenylcarbamate (227.9mg, 1.13 mmol) and 1-(3, 5-dimethylphenyl) piperazine (215mg, 1.13mmol) were mixed in anhydrous THE (20mu), and then DBU (0. 22m#, 1.35mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 10, v/v) to give 261.4mg (Yield 68.0%) of the title compound as a solid. m. p.: 68-72°C 'H NMR (300MHz, CDC13) : 6 ppm 6.74 (d, 1H, J=7.5Hz), 6.59 (s, 3H), 3.76 (d, 4H), 3.20 (t, 4H, J=4. 95Hz, J=5. 13Hz), 2.29 (s, 6H) Example 55 Synthesis of 1- [ (IH-imidazol-1-yl) carbonyll-4- (3, 5-dimethylphenyl) piperazine 1, 1'-Carbonyldiimidazole (81mg, 0.53mmol) and 1- (3, 5-dimethylphenyl) piperazine (105mg, 0.53mmol) were mixed in anhydrous THF (lOIrQ), and then DBU (80µ#, 0.53mmol) was added dropwise to this reaction solution. After stirring for 6 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2 : 1, v/v) to give 69mg (Yield 48. 3%) of the title compound.

'H NMR (300MHz, CDCl3) : 6 ppm 7.90 (s, 1H), 7.23 (s, 1H), 7.11 (s, 1H), 6.52 (m, 3H), 3.75,3.22 (2m, 8H), 2.26 (s, 6H)

Example 56 Synthesis of 1- [ (lH-imidazol-1-yl) thiocarbonyl]-4- (3, 5-dimethylphenyl) piperazine 1, 1'-Thiocarbonyldiimidazole (51.4mg, 0.29mmol) and 1- (3, 5-dimethylphenyl) piperazine (54.9mg, 0.29mmol) were mixed in anhydrous THF (10m#), and then DBU (430, 0.29mmol) was added dropwise to this reaction solution. After stirring for 6 hours at room temperature, the product was extracted with ethyl acetate (50mex3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2: 1, v/v) to give 59.5mg (Yield 68.6%) of the title compound. m. p.: 103-105°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.90 (s, 1H), 7.24 (s, 1H), 7.11 (s, 1H), 6.56 (m, 3H), 4.07,3.29 (2m, 8H), 2.29 (s, 6H) Example 57 Synthesis of l- [ (1H-imidazol-1-yl) carbonyl]-4- (3, 5-dimethylphenyl) piperazine hydrochloride l-[(iH-imidazol-l-yl) carbonyl]-4-(3,5-dimethylphenyl) piperazine (39.8mg, 0.13 mmol) prepared in Example 55 was dissolved in anhydrous methylene chloride (10m#) and the resulting solution was saturated with HC1 gas for 2 hours at 0°C. The saturated solution was allowed to stand for 2 days at 4 °C and the resulting yellow solid was filtered to give 35mg (Yield 78.7%) of the title compound. m. p.: 170-172°C 'HNMR (500MHz, DMSO): 8 ppm 9. 70 (s, 1H), 8.14 (s, 1H), 7.88 (s, 1EI), 7.12 (s, 2H), 6.86 (s, 1H), 3.90 (s, 4M, 3.55 (s, 4H), 2.31 (6H, Me)

13C NMR (125.8MHz, CDCl3+DMSO) : 8 ppm 147.14,138.76,138.68,136.51, 120.85,120.22,116.37,50.47,44.51,21.10,21.03 EI MS, m/e = 320 Example 58 Synthesis of 1-[(lH-imidazol-1-yl) carbonyl]-4-(3, 5-dimethoxyphenyl) piperazine 1,1'-Carbonyldiimidazole (4lmg, 0. 25mmol) and 1- (3, 5-dimethoxyphenyl) piperazine (55. 5mg, 0.25mmol) were mixed in anhydrous THF (lOmQ), and then DBU (480, 0.32mmol) was added dropwise to this reaction solution. After stirring for 3 hours at room temperature, the product was extracted with ethyl acetate (50maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=20: 1, v/v) to give 46mg (Yield 58.2%) of the title compound.

1H NMR(300MHz, CDCl3) : 6 ppm 7.96 (s, 1H), 7.23 (s, 1H), 7.11 (s, 1H), 6.08 (m, 3H), 3.75 (s, 6H), 3.73,3.23 (2m, 8H) Example 59 Synthesis of 1- [ (lH-imidazol-1-yl) carbonyl]-4- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine 1, 1'-Carbonyldiimidazole (25.5mg, 0.16mmol) and 1- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine (43.3mg, 0.16mmol) were mixed in anhydrous THF (4mu), and then DBU (23. 9µ#, 0.16mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (30aux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was

separated by column chromatography (eluent: ethyl acetate: hexane=4: 1, v/v) to give 37. lmg (Yield 63.9%) of the title compound. m. p.: 78-82 °C 'HNMR (300MHz, CDC13) : # ppm 7.91 (s, 1H), 7.23 (s, 1H), 7.12 (s, 1H), 5.84- 5.97 (m, 2H), 5.21 (dd, 2H, J=17. 1Hz, J=1.47Hz), 5.10-5.13 (s, 2H), 5.11 (dd, 2H, J=10.26Hz, J=1.47Hz), 4.00 (s, 4H), 3.87 (s, 4H), 3.63 (t, 4H) Example 60 Synthesis of 1- [ (lH-imidazol-1-yi) thiocarbonyl]-4- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine 1, l'-Thiocarbonyldiimidazole (36.2mg, 0.2mmol) and 1- (4, 6-bis-allylamino- [1, 3,5] triazin-2-yl) piperazine (55.9mg, 0.2mmol) were mixed in anhydrous THF (4m#), and then DBU (30.3/9,0. 2mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent : ethyl acetate: hexane=4: 1, v/v) to give 35.6mg (Yield 45.5%) of the title compound. m. p.: 124-127°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.90 (s, 1H), 7.22 (s, 1H), 7.11 (s, 1H), 5.84- 5.96 (m, 2H), 5.09-5.24 (m, 2H), 5.20 (dd, 2H, J=17.13Hz, J=1.29Hz), 5.11 (dd, 2H, J=10.17Hz, J=1.29Hz), 3.92-4.00 (m, 12H) Example 61 Synthesis of 1-[(1GH-imidazol-1-yl)carbonyl]-4-(4,6-bis-diallylamino-[1,3 ,5] triazin-2-yl) piperazine 1, 1'-Carbonyldiimidazole (34.0mg, 0.23mmol) and 1-(4,6-bis-diallylamino-[1, 3,5]

triazin-2-yl) piperazine (74.6mg, 0. 21mmol) were mixed in anhydrous THF (2mut), and then DBU (34.5NQ, 0.23mmol) was added dropwise to this reaction solution. After stirring for 29 hours at room temperature, the product was extracted with ethyl acetate (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 1, v/v) to give 74.5mg (Yield 79%) of the title compound. m. p.: 94-95 °C 'H NMR (300MHz, CDCI3) : S ppm 7.89 (s, 1H), 7.21 (s, 1H), 7.11 (s, 1H), 5.75- 5.88 (m, 4H), 5.13 (dd, 4H, J=8.43Hz, J=1.47Hz), 5.09 (s, 4H), 4.13 (d, 8H, J=5.67Hz), 3.86 (t, 4H), 3.61 (t, 4H) "C NMR (125.8MHz, CDC1,) : 6 ppm 165.49,165.26,151.07,136.93,134.42, 129.88,117.90,116.29,48.38,46.43,42.93 EI MS, m/e = 449 Example 62 Synthesis of 1-[(lH-imidazol-l-yl) carbonyl]-4-(4, 6-bis-cyclopropylmethyl amino- [1, 3,5] triazin-2-yl) piperazine 1, 1'-Carbonyldiimidazole (35. 3mg, 0.22mmol) and 1- (4, 6-bis- cyclopropylmethylamino- [1, 3,5] triazin-2-yl) piperazine (60mg, 0.2mmol) were mixed in anhydrous THF (4m#), and then DBU (29. 6µ#, 0. 2mmol) was added dropwise to this reaction solution. After stirring for 16 hours at room temperature, the product was extracted with ethyl acetate (30mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=9: 1, v/v) to give 59.6mg (Yield 75.0%) of the title compound. m. p.: 132-133°C

1H NMR(500MHz, CDCl3) : 6 ppm 7.90 (s, 1H), 7.23 (s, 1H), 7.12 (s, 1H), 4.95 (s, 2H), 3.87 (s, 4H), 3.21 (dd, 4H), 0.93-1.06 (m, 2H), 0.50 (dt, 4H), 0. 23 (dt, 4H) 13C NMR (125.8MHz, CDCl3) : # ppm 166.10,165.22,151.03,136.94,129.90, 117.92,46.44,45.69,42.77,10.99,3.36 EI MS, m/e = 397 Example 63 Synthesis of 1-[(1H-imidazolo-1-yl)carbonyl]-4-p{4,6-bis[ethyl-(2-methyla llyl) aminol- [1, 3,5] triazin-2-yl}piperazine 1, 1'-Carbonyldiimidazole (35. 9mg, 0.24mmol) and 1-{4,6-bis-[ethyl-(2- methylallyl) amino]- [1, 3,5] triazin-2-yl} piperazine (79.5mg, 0.22mmol) were mixed in anhydrous THF (4m#), and then DBU (33.1,0. 22mmol) was added dropwise to this reaction solution. After stirring for 15.5 hours at room temperature, the product was extracted with ethyl acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 1, v/v) to give 84.9mg (Yield 84.7%) of the title compound.

'H NMR (300MHz, CDCl3) : 6 ppm 7.90 (s, IH), 7.23 (s, 1H), 7.11 (s, 1H), 4.79 (d, 4H), 4.11 (s, 4H), 3.86 (s, 4H), 3.63 (s, 4H), 3.49 (s, 4H), 1.68 (s, 6H), 0.90 (t, 6H) Example 64 Synthesis of 1-[(1H-imidazol-1-yl)carbonyl]-4-[4,6-bis-(allyl-cyclohexyl- amino)- [l3S5] triazin-2-yl] piperazine 1, 1'-Carbonyldiimidazole (20.9mg, 0.13mmol) and 1- [4, 6-bis- (allyl-cyclohexyl- amino)- [1, 3,5] triazin-2-yl] piperazine (51. 5mg, 0.12mmol) were mixed in anhydrous THF (4 m#), and then DBU (17. 5/, 0. 12mmol) was added dropwise to this reaction solution. After

stirring for 15 hours at room temperature, the product was extracted with ethyl acetate (30 m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2 : 1, v/v) to give 50. 5mg (Yield 80.8%) of the title compound. m. p.: 132-135°C 1H NMR(300MHz, CDCl3) : 8 ppm 7.90 (s, 1H), 7.23 (s, 1H), 7.12 (s, 1H), 5.87 (m, 2H), 5.12 (d, 2H, J=17. 4Hz), 5.02 (d, 2H, J=10. 08Hz), 4.44 (s, 2H), 4.06 (d, 4H), 3.84 (s, 4H), 3.62 (s, 4H), 1. 09-1.78 (m, 10H) Example 65 Synthesis of 1-[(lE-imidazol-1-yl) carbonyl]-4-{4, 6-bis-(2, 5-dihydropyrrol-1- yl)- [1, 3,5] triazin-2-yl} piperazine 1, 1'-Carbonyldiimidazole (30.6mg, 0.19mmol) and 1-{4,6-bis-(2, 5-dihydropyrrol- 1-yl)- [1, 3,5] triazin-2-yl} piperazine (51.4mg, 0.17mmol) were mixed in anhydrous THF (4 m#), and then DBU (25. 7µ#, 0.17mmol) was added dropwise to this reaction solution. After stirring for 18 hours at room temperature, the product was extracted with ethyl acetate (30 m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=2 : 1, v/v) to give 64.0mg (Yield 94.8%) of the title compound. m. p.: 160-162°C 'H NMR (300MHz, CDC13) : 6 ppm 7.91 (s, 1H), 7.23 (s, 1H), 7.12 (s, 1H), 5.87 (t, 4H), 4. 29 (d, 8H, J=2. 73Hz), 3.91 (t, 4H), 3.64 (t, 4H) Example 66 Synthesis of 3- [ (lH-imidazol-l-yl) carbonyl]-7, 8-dimethoxy-l-phenyl-2, 3, 4, 5- tetrahydro-3H-benzazepine

1, 1'-Carbonyldiimidazole (1. 75g, 10. 8mmol) and 7,8-dimethoxy-1-phenyl-2,3,4,5- tetrahydro-3H-benzazepine (3.06g, 10. 8mmol) were mixed in anhydrous THF (40mA), and then DBU (1. 8mut, 11. 9mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (100mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=10: 1, v/v) to give 3.01g (Yield 73.8%) of the title compound. m. p.: 132-133°C 'H NMR (500MHz, CDCl3) : 6 ppm 7.63 (s, 1H), 7.23-7.32 (m, 4H), 7.02-7.03 (m, 4H), 6.66 (s, 1H), 6.55 (s, 1H), 4.62 (s, 1H), 4.08-4.13 (m, 2H), 3.89 (s, 3H), 3.75-3.78 (m, 1H), 3.76 (s, 3H), 3.60 (m, 1H), 3.23 (m, IM, 2.86 (d, 1H) 13C NMR (125.8MHz, CDCl3) : 6 ppm 151.85,148.03,147.71,136.75,131.80, 129.52,128.86,127.72,126.95,117.88,114.56,113.62,56.00,55.91 ,51.37,50.53,49.62, 34.01 EI MS, m/e = 377 Example 67 Synthesis of 3- [ (1H-imidazol-1-yl) thiocarbonyl]-7, 8-dimethoxy-1-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Thiocarbonyldiimidazole (50.3mg, 0.28mmol) and 7,8-dimethoxy-1-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine (80mg, 0.28mmol) were mixed in anhydrous THF (10 mA), and then DBU (42tA, 0.28mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (50 maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1:9,

v/v) to give 75.5mg (Yield 68.5%) of the title compound. m. p.: 124-125°C 'H NMR (300MHz, CDCl3) : # ppm 7.55 (s, 1H), 7.22-7.33 (m, 4H), 6.97-7.02 (m, 4H), 6.63 (s, 1H), 6.55 (s, 1H), 4.20 (dd, IH, J=13. 7Hz), 3.67-3.88 (m, 3H), 3.88 (s, 3H), 3.75 (s, 3H), 3.31 (s, 1H), 2.88 (s, 1H) Example 68 Synthesis of 3- [ (lH-imidazol-1-yl) carbonyl]- (R)-7, 8-dimethoxy-1-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (133.9mg, 0.56mmol) and (R)-7,8-dimethoxy-1-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine (153.7mg, 0.56mmol) were mixed in anhydrous THF (3 mut), and then DBU (84.3/A, 0.56mmol) was added dropwise to this reaction solution. After stirring for 18 hours at room temperature, the product was extracted with ethyl acetate (50 m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=10: 1, v/v) to give 170mg (Yield 79.8%) of the title compound. m. p.: 112-114°V 'H NMR (500MHz, CDGl3) : 6 ppm 7. 63 (s, 1H), 7.23-7.32 (m, 4H), 7.02-7.03 (m, 4H), 6.66 (s, 1H), 6.55 (s, 1H), 4.62 (s, 1H), 4.08-4.13 (m, 2H), 3.89 (s, 3H), 3.75-3.78 (m, 1H), 3.76 (s, 3H), 3.60 (m, 1H), 3.23 (m, 1H), 2.86 (d, 1H) 13C NMR (125. 8MHz, CDCl3) : 6 ppm 151.85,148.03,147.71,136.75,131.80, 129.52,128.86,127.72,126.95,117.88,114.56,113.62,56.00,55.91 ,51.37,50.53,49.62, 34.01 EI MS, m/e = 377 Example 69 Synthesis of 3-[(1G-imidazol-1-yl)carbonykl]-(S)-7,8-dimethoxy-1-phenyl-

2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (48.1mg, 0.20mmol) and (S)-7,8-dimethoxy-1-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine (55.2mg, 0.20mmol) were mixed in anhydrous THF (3 mut), and then DBU (30.3, ut, 0 20mmol) was added dropwise to this reaction solution. After stirring for 20 hours at room temperature, the product was extracted with ethyl acetate (30 maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=10 : 1, v/v) to give 52.3mg (Yield 69.3%) of the title compound. m. p.: 131-132°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.63 (s, 1H), 7.23-7.32 (m, 4H), 7.02-7.03 (m, 4H), 6.66 (s, 1H), 6.55 (s, 1H), 4.62 (s, IM, 4.08-4.13 (m, 2H), 3.89 (s, 3H), 3.75-3.78 (m, 1H), 3. 76 (s, 3H), 3.60 (m, 1H), 3.23 (m, 1H), 2.86 (d, 1H) Example 70 Synthesis of 3- [ (lH-imidazol-1-yl) carbonyl]-7, 8-dimethoxy-1- (4-fluoro) phenyl -2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (27. 1mg, 0.17mmol) and 7, 8-dimethoxy-1-(4- fluoro) phenyl-2,3,4,5-tetrahydro-3H-benzazepine (50.3mg, 0.17mmol) were mixed in anhydrous THF (2m#), and then DBU (25 ut, 0.17mmol) was added dropwise to this reaction solution. After stirring for 22 hours at room temperature, the product was extracted with ethyl acetate (30m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol =20: 1, v/v) to give 35. lmg (Yield 53.2%) of the title compound. m. p.: 145-147 °C 'H NMR 9500MHz, CDCl3) : 6 ppm 7.68 (s, 1H), 6.98-7.05 (m, 6H), 6.65 (s, 1H),

6.52 (s, IM, 4.60 (t, 1H), 4.04-4.13 (m, 2H), 3.89 (s, 3H), 3.75-3.77 (m, 4H), 3.62 (m, 1H), 3.20 (m, 1H), 2.84 (m, 1H) 13C NMR (125.8MHz, CDCl3) : 8 ppm 162.60,160.85,151.77,148.02,147.71, 137.90,136.87,131.56,129.56,129.23,129.17,117.83,115.72,115. 55,114.34,113.57, 55.93,55.86,50.89,49.75,49.58,33.95 EI MS, m/e = 395 Example 71 Synthesis of 3- [ (IH-imidazol-1-yl) carbonyll-7, 8-dimethoxy-l- (4-chloro) phenyl -2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (30.2mg, 0.19mmol) and 7,8-dimethoxy-l- (4-chloro) phenyl-2, 3,4,5-tetrahydro-3H-benzazepine (59.1mg, 0.19mmol) were mixed in anhydrous THF (3mA), and then DBU (27. 8µ#, 0.19mmol) was added dropwise to this reaction solution.

After stirring for 16 hours at room temperature, the product was extracted with ethyl acetate (30mQx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride : methanol =20: 1, v/v) to give 49mg (Yield 64.0%) of the title compound. m. p.: 147-149°C 'H NMR (500MHz, CDCl3) : 6 ppm 7.68 (s, 1H), 6.96-7.28 (m, 6H), 6.65 (s, 1H), 6.53 (s, 1H), 4.61 (t, 1H), 4.07 (m, 2H), 4.03 (s, 3H), 3. 77 (m, 4H), 3.58 (m, 1H), 3.19 (m, 1H), 2.83 (m, 1H) 13C NMR (125.8MHz, CDCl3) : # ppm 151.67,147.96,147.68,136.60,132.62, 131.09,129.46,128.96,128.82,117.76,114.27,113.51,55.84,55.80 ,50.89,49.76,49.58, 33.81 EI MS, m/e = 411 Example 72

Synthesis of 3- [ (IH-imidazol-1-yl) carbonyll-8-methoxy-l-phenyl-2, 3,4,5- tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (105.7mg, 0.65mmol) and 8-methoxy-l-phenyl- 2,3,4,5-tetrahydro-3H-benzazepine (150.1mg, 0.59mmol) were mixed in anhydrous THF (4 mQ), and then DBU (88.6, fl, 0.59mmol) was added dropwise to this reaction solution. After stirring for 18 hours at room temperature, the product was extracted with ethyl acetate (50 mix3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=9 : 1, v/v) to give 173. lmg (Yield 84.5%) of the title compound. m. p.: 65-68°C 'H NMR (500MHz, CDCl3) : 6 ppm 7.63 (s, 1H), 7.24-7.30 (m, 3H), 7.02-7.10 (m, 5H), 6.76 (d, 1H), 6.59 (s, 1H), 4.61 (s, 1H), 4.10 (m, 2H), 3.73 (m, 4H), 3.59 (m, 1H), 3.18 (m, 1H), 2.91 (m, 1H) EI MS, m/e = 347 Example 73 Synthesis of 3- [ (lH-imidazoI-l-yl) carbonyl]-8-methoxy-l- (4-fluoro) phenyt- 2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (60.6mg, 0.37mmol) and 8-methoxy-l- (4-fluoro) phenyl- 2,3,4,5-tetrahydro-3H-benzazepine (92.6mg, 0.34mmol) were mixed in anhydrous THF (3 mA), and then DBU (50. 8µ#, 0.34mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with ethyl acetate (50 maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=4 : 1, v/v) to give 79.6mg (Yield 63.9%) of the title compound.

m. p.: 65-69 °C 'H NMR (500MHz, CDCl3) : 6 ppm 7.67 (s, 1H), 6.99-7.10 (m, 7H), 6.76 (d, 1H), 6. 56 (s, 1H), 4. 60 (s, 1H), 4.07 (m, 2H), 3.74 (m, 4H), 3.59 (m, 1H), 3.14 (m, 1H), 2.01 (m, 1H) Example 74 Synthesis of 3-[(lE-imidazol-l-yl) carbonyl]-8-methoxy-1-(4-chloro) phenyl- 2,3,4,5-tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (99.6mg, 0.61mmol) and 8-methoxy-l- (4-chloro) phenyl- 2,3,4,5-tetrahydro-3H-benzazepine (176.8mg, 0.61mmol) were mixed in anhydrous THF (3 mua), and then DBU (91. 8, uQ, 0.61mmol) was added dropwise to this reaction solution. After stirring for 16 hours at room temperature, the product was extracted with ethyl acetate (50 maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was separated by column chromatography (eluent: ethyl acetate: hexane=9: 1, v/v) to give 170mg (Yield 79.8%) of the title compound. m. p.: 66-70°C 1H NMR (500MHz, CDCl3) : # ppm 7.68 (t, 1H), 7.25-7.29 (m, 2H), 6.98-7.10 (m, 5H), 6.76 (dd, 1H, J=2.68Hz, J=8. 24Hz), 6.56 (d, 1H, J=2. 68Hz), 4.60 (t, 1fI), 4.07 (m, 2H), 3.74 (m, 4H), 3.60 (m, 1H), 3.14 (m, 1H), 2.90 (m, 1H) Example 75 Synthesis of 3-[(1H-imidazol-1-yl)carbonyl]-1-phenyl-2, 3,4,5-tetrahydro-3H- benzazepine 1, 1'-Carbonyldiimidazole (79.1mg, 0.49mmol) and 1-phenyl-2, 3,4,5-tetrahydro- 3H-benzazepine (109. Omg, 0. 49mmol) were mixed in anhydrous THF (3m#), and then DBU (73, ut, 0.49mmol) was added dropwise to this reaction solution. After stirring for 21

hours at room temperature, the product was extracted with ethyl acetate (50maux3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=9 : 1, v/v) to give 150. 9mg (Yield 97.1 %) of the title compound. m. p. : 98-99 °C 'H NMR (300MHz, CDCl3) : 6 ppm 7.62 (s, 1H), 7.18-7.32 (m, 6H), 7.01-7.03 (m, 5H), 4. 67 (t, 1H), 4.06-4.20 (m, 2H), 3.76 (m, 1H), 3.62 (m, 1H), 3.25 (m, 1H), 2.96 (m, 1H) Example 76 Synthesis of 3- [ (IH-imidazol-1-yl) carbonyl]-1- (4-fluoro) phenyl-2, 3,4,5- tetrahydro-3H-benzazepine 1, 1'-Carbonyldiimidazole (82.4mg, 0. 51mmol) and 1- (4-fluoro) phenyl-2,3,4,5-tetra hydro-3H-benzazepine (112mg, 0.46mmol) were mixed in anhydrous THF (3me), and then DBU (69µ#, 0. 46mmol) was added dropwise to this reaction solution. After stirring for 17 hours at room temperature, the product was extracted with ethyl acetate (50m3x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=9 : 1, v/v) to give 147.7mg (Yield 95.5%) of the title compound. m. p.: 65-68 °C 'H NMR (300MHz, CDCl3) : 5 ppm 7.65 (s, 1H), 7.19-7.26 (m, 3H), 7.00-7.04 (m, 7H), 4.65 (s, 1H), 4.09 (m, 2H), 3.76 (m, 1H), 3.61 (m, 1H), 3.21 (m, 1H), 2.95 (m, 1H) Example 77 Synthesis of 3--imidazol-1-yl) carbonyl]-1-(4-chloro) phenyl-2, 3,4,5- tetrahydro-3H-benzazepine

1, 1'-Carbonyldiimidazole (47.9mg, 0.30mmol) and 1- (4-chloro) phenyl-2,3,4,5- tetrahydro-3H-benzazepine (76.1mg, 0.30mmol) were mixed in anhydrous THF (3mu), and then DBU (44, u, , 0.30mmol) was added dropwise to this reaction solution. After stirring for 19 hours at room temperature, the product was extracted with ethyl acetate (50m#x3).

The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride : methanol=20 : 1, v/v) to give 89.5mg (Yield 86.2%) of the title compound. m. p.: 60-64 °C 'H NMR (300MHz, CDC13) : 6 ppm 7.66 (s, 1H), 6.96-7.28 (m, 10H), 4.65 (s, 1H), 4.10 (m, 2H), 3.78 (m, 1H), 3.61 (m, 1H), 3.20 (m, 1H), 2.94 (m, 1H) Example 78 Synthesis of 3- [ (lH-imidazol-1-yl) carbonyl]-7, 8-dihydroxy-1-phenyl-2, 3,4,5- tetrahydro-3H-benzazepine 3-[(1H-imidazol-1-yl)carbonyl]-7,8-dimethoxy-1-phenyl-2, 3,4,5-tetrahydro-3H- benzazepine (200mg, 0.53mmol) prepared in Example 66 was dissolved in anhydrous methylene chloride (1. 8nA) and the resulting solution was slowly added dropwise to BBr3 (0.25me, 2.65mmol) dissolved in anhydrous methylene chloride (O. 8m#) at 15°C. The reaction solution was stirred for 3 hours at 25°C, the temperature was cooled to-30°C, and then methanol (1. 6mQ) was added to the reaction mixture. The organic solution was concentrated under reduced pressure and the residue was extracted with ethyl acetate (50m# x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol= 10: 1, v/v) to give 177.6mg (Yield 96%) of the title compound. m. p.: 148-150°C 'H NMR (500M : Hz, CDCl3) : 6 ppm 7.62 (s, 1H), 7.21-7. 26 (m, 3H), 6.99-7.03 (m,

4H), 6.67 (s, 1H), 6.53 (s, 1H), 4.52 (s, 1H), 4.11 (m, 2H), 3.92 (m, 1H), 3.66 (2H, OH), 3.56 (m, 1H), 3.12 (m, 1H), 2.78 (m, 1H) Example 79 Synthesis of 3- [ (lH-imidazol-1-yl) carbonyl]-7, 8-diethoxy-1-phenyl-2, 3,4,5- tetrahydro-3H-benzazepine 3- [ (IH-imidazol-1-yl)carbonyl]-7,8-dihydroxy-1-phenyl-2,3,4,5-t etrahydro-3H- benzazepine (90mg, 0.26mmol) prepared in Example 78 and ethyl iodide (43.3, tt, 0.54mmol) were mixed in anhydrous DMF (30), and then NaH (60%, 21.7mg, 0.54mmol) was added dropwise to this reaction solution. After stirring for 4.5 hours at room temperature, the product was extracted with ethyl acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent : ethyl acetate: hexane=9: 1, v/v) to give 62.2mg (Yield 59. 0%) of the title compound. m. p.: 59-60 °C 'H NMR (500MHz, CDCl3) : # ppm 7, 62 (s, 1H), 7.23-7.29 (m, 3H), 7.00-7.03 (m, 4H), 6.67 (s, 1H), 6.55 (s, 1H), 4.57 (s, 1H), 4.09 (m, 4H), 3.95 (q, 2H), 3.72 (m, 1H), 3.59 (m, 1H), 3.17 (m, 1H), 2.85 (m, 1H), 1.45 (t, 3H), 1.36 (t, 3H) EI MS, m/e = 405 Example 80 Synthesis of 1- [ (lH-imidazol-l-yl) carbonyl]-4, 4-diphenyl-piperidine 1, 1'-Carbonyldiimidazole (40mg, 0.25mmol) and 4,4-diphenyl-piperidine (49mg, 0.25mmol) were mixed in anhydrous THF (3n4), and then DBU (84.3, aQ, 0.56mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (50mix3). The organic solution was washed with

aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 1, v/v) to give 48mg (Yield 58%) of the title compound. m. p. : 179-182°C 'H NMR (300MHz, CDCl3) : 6 ppm 7.86 (s, 1H), 7.67 (s, 1H), 7.09-7.34 (m, 11H), 3.67 (t, 3H, J=5.49Hz), 2.50 (t, 3H, J=5.49Hz) Example 81 Synthesis of 1- [ (lH-imidazol-1-yl) thiocarbonyl]-4, 4-diphenyl-piperidine 1, 1'-Thiocarbonyldiimidazole (45mg, 0.25mmol) and 4,4-diphenyl-piperidine (49mg, 0.25mmol) were mixed in anhydrous THF (3mu), and then DBU (84.3, ut, 0.56mmol) was added dropwise to this reaction solution. After stirring for 4 hours at room temperature, the product was extracted with ethyl acetate (50m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: ethyl acetate: hexane=1 : 1, v/v) to give 56mg (Yield 64.5%) of the title compound. m. p.: 161-165°C 'H NMR (300MHz, CDCl3) : 8 ppm 7.84 (s, 1H), 7. 08-7.35 (m, 12H), 3.97 (s, 3H), 2.50 (s, 3H) Example 82 Synthesis of 1- [ (IH-imidazol-1-yl) carbonyll-4-ethoxycarbonyl-4-phenyl- piperidine l-[(lH-imidazol-1-yl) carbonyl]-4-hydroxycarbonyl-4-phenyl-piperidine (50mg, 0. 17mmol) and 95% sulfuric acid (10/, 0. 17mmol) were mixed in absolute ethanol (5n4),

and stirred under reflux for 5 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=30 : 1, v/v) to give 12.2mg (Yield 21.9%) of the title compound.

'H NMR (300MHz, CDCl3) : # ppm 7.87 (s, 1H), 7.27-7.37 (m, 5H), 7.19 (s, 1H), 7.10 (s, 1H), 4.17 (q, 2H), 4.05 (m, 2H), 3.32 (m, 2H), 2.67 (m, 2H), 2.03 (m, 2H), 1.18 (t, 3H) Example 83 Synthesis of 1- [ (IH-imidazol-1-yl) carbonyll-4- [ (methoxycarbonyl)- (4-methoxy phenyl)-methyl]-piperazine 1, 1'-Carbonyldiimidazole (20mg, 0.13mmol) and 4- [ (methoxycarbonyl)- (4- methoxy phenyl)-methyl]-piperazine (35mg, 0.13mmol) were mixed in anhydrous THF (5 m#), and then DBU (32µ#, 0.21mmol) was added dropwise to this reaction solution. After stirring for 12 hours at room temperature, the product was extracted with methylene chloride (30m#x3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=30 : 1, v/v) to give 37mg (Yield 79.2%) of the title compound. lH NE (300MHz, CDCl3) : 6 ppm 7.85,7.18, 7. 09 (3s, 3H), 7.24,6.87 (2d, 4H, J=9Hz), 3.79,3.65 (2s, 6H), 3.79,3.58,3.19,2.64,2.58 (5m, 9H) Example 84 Synthesis of 1- [ (IH-imidazol-1-yl) carbonyll-4- (diphenylmethyl) piperazine 1, 1'-Carbonyldiimidazole (41mg, 0.25mmol) and 1- (diphenylmethyl) piperazine (64mg, 0.25mmol) were mixed in anhydrous THF (10m#), and then DBU (48, ue, 0. 32mmol) was added dropwise to this reaction solution. After stirring for 2 hours at room temperature, the product was extracted with ethyl acetate (50m. ex3). The organic solution was washed

with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=20: 1, v/v) to give 65mg (Yield 75. 1%) of the title compound.

'H NMR (300MHz, CDCl3) : 6 ppm 7.83,7.22,7.11 (3s, 3H), 7.40-7.27 (m, 10H), 4.28 (s, 1H), 3.60,2.46 (2m, 8H) Example 85 Synthesis of 5- [ (IH-imidazol-1-yl) carbonyll-10, 11-dihydro-5H-dibenzazepine 1, 1'-Carbonyldiimidazole (415mg, 2.5mmol) and 10, 11-dihydro-5H-dibenzazepine (500mg, 2.5mmol) were mixed in anhydrous THF (lone), and then 95% NaH (415mg, 2.5mmol) was added dropwise to this reaction solution. After stirring under reflux for 19 hours at 80°C, the product was extracted with diethylether (100mAx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=5 : 1, v/v) to give 22mg (Yield 3.0%) of the title compound. m. p. : 189-190°C 'H NMR (300MHz, CDCl3) : # ppm 7.64 (s, 1H), 7.19-7.28 (m, 8H), 6.95 (s, 1H), 6.87 (s, IM, 3.54 (br-m, 2H), 3.03 (br-m, 2H) Example 86 Synthesis of 4- [ (1H-imidazol-1-yl) carbonyl]-1, 2,3,5-tetrahydro-4H-benzo [1, 4j diazepine 2,3,4,5-Tetrahydro-lH-benzofl, 4] diazepine (238.7mg, 1. 6mmol) and 95% NaH (44.8mg, 1.77mmol) were mixed in anhydrous THF (8mA) and stirred for 30 minutes at room temperature. To this reaction solution was added dropwise 1, 1'-carbonyldiimidazole

(259.2mg, 1. 6mmol), and the resulting mixture was stirred for 2.5 hours at room temperature. The product was extracted with diethylether (50mEx3). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=100 : 1, v/v) to give 65. 8mg (Yield 17.0%) of the title compound. m. p. : 98-101°C IH NMR (500MHz, CDCl3) : 6 ppm 6.64-7.15 (m, 7H), 4.34 (s, 2H), 4.29 (m, 2H), 3.43 (m, 2H) Example 87 Synthesis of 6-[(lH-imidazol-l-yl) carbonyl]-8-phenyl-4, 5,7,8-tetrahydro-6H- thieno [2,3] azepine 8-Phenyl-4,5,7,8-tetrahydro-6H-thieno [2,3] azepine (46.1mg, 0. 2mmol) and 95% NaH (14.4mg, 0.6mmol) were mixed in anhydrous THF (lm4) and stirred for 30 minutes at room temperature. To this reaction solution was added dropwise 1, 1'-carbonyldiimidazole (32.6mg, 0.2mmol), and the resulting mixture was stirred for 1 hour at room temperature.

The product was extracted with methylene chloride (50mx4). The organic solution was washed with aqueous sodium chloride solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluent: methylene chloride: methanol=30 : 1, v/v) to give 30.7mg (Yield 47.5%) of the title compound. m. p.: 152-154 °C 'H NMR (50OMHz, CDCl3) : 6 ppm 7.54 (s, 1H), 6.82-7.29 (m, 9H), 4.58 (m, 1H), 4.17 (dd, 1H, J=14.1, J=7.32Hz), 4.06 (dd, 1H, J=14. 1, J=3.48Hz), 3.79 (m, 1H), 3.71 (m, 1H), 3.26 (m, 1H), 3.05 (m, 1H) INDUSTRIAL APPLICABILITY

Experiment 1: Anti-cancer activity The anti-cancer activity and toxicity of the compound according to the present invention were evaluated in vitro using A549 (lung cancer), SUN638 (gastric cancer), HCT116 (rectal cancer), and A431 (ovarian cancer) cell lines. The above four (4) cell lines were purchased from Cancer Research Institute, Seoul National University College of Medicine. The compounds prepared in the Examples according to the present invention were used as the test compound, and the known cisplatin was used as the control compound. The experiment was basically carried out according to the process described in Monks, A., et al, Journal of National Cancer Institute. 83: 757-766 (1991) and the results are represented in the following Tables 2 and 3.

Table 2 Compound A549 Cell Line (/g/) SUN6 8 Cell Lme (gM) No. GI50 TGI50 LC50 GI50 TGI50 LC50 1 1.21 39.81 >100 1.99 7.07 >100 3 1. 31 5. 62 >100 1. 47 9. 33 >100 4 1. 20 100 >100 1. 86 6. 76 >100 5 2. 08 46. 98 >100 1. 69 6. 16 >100 6 2. 69 100 >100 1. 90 6. 91 >100 7 3. 38 100 >100 2. 45 7. 41 >100 16 1.02 63.09 >100 0.15 35.48 >100 17 6. 45 83. 17 >100 0. 63 39. 81 >100 26 1. 36 100 >100 2. 51 95. 49 >100 28 1. 31 34. 67 >100 1. 99 7. 07 >100 38 1. 28 4. 36 >100 2. 75 100 >100 48 1. 07 72. 44 >100 1. 62 35. 48 >100 53 2. 75 8. 91 >100 2. 18 5. 49 >100 55 1. 77 25. 70 >100 1. 09 6. 91 >100 56 2. 04 12. 30 >100 1. 34 6. 62 >100 57 1. 77 15. 13 >100 1. 69 6. 91 >100 58 2. 75 100 >100 2. 39 7. 76 >100 61 6. 02 32. 35 >100 2. 95 6. 91 >100 62 0.48 42.65 >100 0.61 28.18 >100 63 2. 23 4. 89 >100 1. 81 5. 12 >100 66 0. 38 54. 95 >100 0. 21 1. 73 >100 Table 2 (continued) Compound A549 Cell Line(µg/m#) SUN638 Cell Lineg/mA) No. GI50 TGI50 LC50 GI50 TGI50 LC50 67 0.66 17.78 >100 1.51 8.12 >100 68 0. 23 100 >100 0. 22 97. 72 >100 69 0. 36 97. 72 >100 0. 13 3. 63 >100 70 1.12 100 >100 1.78 7.24 >100 71 4. 78 93. 32 >100 2. 63 9. 12 >100 72 2.23 100 >100 1.44 7.24 >100 80 1. 38 100 >100 1. 62 5. 88 >100 Cisplatin 3. 8 47. 3 >100 1. 7 13. 3 >100

As seen from the result in Table 2 above, the compounds of the present invention show a superior anti-cancer activity in A549 (lung cancer) and SUN638 (gastric cancer) cell lines to the control compound. More specifically, the anti-cancer activity of the compounds of the present invention is as high as or up to 10 times higher than that of the control compound in A549 and SUN638 cell lines.

Table 3 Compound A431 Cell Line(µg/m#) HCT116 Cell Line (µg/m#) No. GI50 TGI50 LC50 GI50 TGI50 LC50 3 2.04 26.30 >100 1.31 5.62 >100 4---0. 12 3.54 >100 5 - - - 0. 15 4.07 >100 6 0. 39 3.31 >100 Table 3 (continued) Compound A431 Cell Line(µg/m#) HCT116 Cell Line(µg/m#) No. GI50 TGI50 LC50 GI50 TGI50 LC50 7 - - - 0.15 4.08 >100 38 1. 41 7. 24 >100 1. 28 4. 36 >100 48 1. 65 100 >100 0. 67 17. 38 >100 55 1. 38 67. 60 >100 2. 08 13. 48 >100 56 1. 31 28. 84 >100 1. 47 6. 02 >100 57 1. 51 8. 31 >100 1. 34 4. 89 >100 58---0. 66 12. 88 >100 62 - - - 0.38 19.05 >100 63---1. 77 4. 78 >100 66 0. 28 100 >100 0. 19 7. 76 >100 67 0. 70 30. 19 >100 0. 23 13. 48 >100 68---0. 24 I0. 96 >100 69---0. 13 10. 71 >100 70---1. 31 23. 98 >100 71---2. 69 14. 12 >100 72---0. 10 9. 42 >100 74 - - - 1.44 7.24 >100 80---1. 47 16. 88 >100 Cisplatin 3.2 28.7 >100 2.9 32.77 >100

Judging from the result in Table 3 above, the compounds of the present invention also show a superior anti-cancer activity in HCT116 (rectal cancer) and A431 (ovarian cancer) cell lines to the control compound. Specifically, the compounds of the present

invention exhibit the same or a maximun of about 30 times higher anti-cancer activity than the control compound in HCTI16 cell line. In A431 cell line, most of the compounds according to the present invention show twice or more higher anti-cancer activity than cisplatin and some compounds show five to eleven times higher activity than the control compound.

Experiment 2: Acute toxicity test The test for acute toxicity was carried out according to Notice No. 1999-61 of KFDA ('Standard for Toxicity Test of Medicines') and to Notice No. 1998-17 of KFDA ('Standard for Safety Control of Medicines') as follows.

1. Test System (1) Test Animal: SPF ICR mouse (2) Age of the Test Animal: 4 weeks from acquisition 5 weeks from the start of administration (3) Gender and Number of Test Animal: respective 18 he and she-mice (6 groups in each of he and she-mice, 3 mice per group) (4) Breeding Environment: Temperature 22 3 °C, Relative humidity 10%, Illumination 150-300 Lux (5) Method of Administration: Single administration per oral (6) Items to be Observed: General symptoms, appearance, weight and autopsy of dead mice (7) Test Compound: Compounds prepared in Examples 2,38,57,61,62,66 and 70 (8) Medium: 0.5% Tween 80 2. Test Result As a result of the 7-day observation after the test compound was administered, no

animals were dead in any test group. The Minimal Lethal Dose of single administration per oral in mouse was determined to be 354.3mg/kg to 2000mg/kg or more in both he and she-mice (see, Table 4). This value is still higher than those of various drugs which are clinically used at the present time, and thus, the compound according to the present invention proved very safe.

Table 4 Test Compound LDso (g/kg) Cisplatin 9. 7 Carboplatin 150 Doxorubicin 21. 1 Compound of Example 2 2000 (male and female) Compound of Example 38 2000 (male and female) Compound of Example 57 1156. 5 (male and female) Compound of Examople 61 2331.7(male) 1143 (female) Compound of Example 62 354. 3 (male) 465. 5 (female) Compound of Example 66 1921 (male) 2000 (female) Compound of Example 70 2000 (male and female)