1,3,4-THIADIAZOLES USEFUL FOR THE TREATMENT OF CMV INFECTIONS

Title:

1,3,4-THIADIAZOLES USEFUL FOR THE TREATMENT OF CMV INFECTIONS

Document Type and Number:

WIPO Patent Application WO/1999/047507

Kind Code:

Abstract:

The present invention presents novel 1,3,4-thiadiazole derivatives of formula (I) which have useful antiviral activity against herpes virus, cytomegalovirus (CMV).

Inventors:

TURNER STEVEN R (US)
THAISRIVONGS SUVIT (US)

Application Number:

PCT/US1999/003744

Publication Date:

September 23, 1999

Filing Date:

March 16, 1999

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Assignee:

UPJOHN CO (US)
TURNER STEVEN R (US)
THAISRIVONGS SUVIT (US)

International Classes:

A61K31/433; A61K31/496; A61K31/5377; A61P31/12; A61P31/22; C07D285/135; C07D417/12; C07D417/14; C07D521/00; C07D285/12; (IPC1-7): C07D285/135; C07D417/12; A61K31/41

Domestic Patent References:

WO1993020814A1

1993-10-28

Foreign References:

EP0785193A1	1997-07-23
EP0229501A1	1987-07-22
EP0061434A1	1982-09-29

Other References:

PATENT ABSTRACTS OF JAPAN vol. 199, no. 510, 30 November 1995 (1995-11-30) & JP 07 188017 A (SOYAKU GIJUTSU KENKYUSHO:KK), 25 July 1995 (1995-07-25)
PATENT ABSTRACTS OF JAPAN vol. 199, no. 509, 31 October 1995 (1995-10-31) & JP 07 149748 A (SOUYAKU GIJUTSU KENKYUSHO:KK), 13 June 1995 (1995-06-13)
FREDERICK KURZER : "Heterocyclic compounds from Urea Derivatives. Part XXI." J. CHEM. SOC. (C),1971, pages 2932-2938, XP002093612 London
TADASHI OKAWARA ET AL.: "A New Route ti 1,2,4-Triazoles and 1,3,4 Thiadiazoles from 1-acylbithiourea" J. HETEROCYCLIC CHEM., vol. 25, 1988, pages 1071-1074, XP002093611 cited in the application

Attorney, Agent or Firm:

Yang X, Lucy (MI, US)
Perry, Robert Edward (Gill Jennings & Every Broadgate House 7 Eldon Street London EC2M 7LH, GB)

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Claims:

WE CLAIM.1. A compound of formula I or pharmaceutically acceptable salts thereof wherein: Yis ora)-NHR1, xiS a)-O-, b) -S(=O)h-, orc)-CH2-, d)-NR2-; R, is alkyl,a)C1-18 cycloalkyl,b)-(CH2)i-C3-7 c)-(CH2)i-bicycloalkyl, d)-(CH2)j-M, e)-(CH2)j-W, f) -(CH2)k aryl, wherein aryl may be substituted with one to three R3, g) -(CH2)k-het, wherein het may be substituted with one to three R3, h) -(CH2)k-Q, wherein Q may be substituted with one to three Ru, or i) H; R2 is a) H, b) C

l. alkyl, c)C (=O) C14 alkyl, d)S (=O) C14 alkyl, alkyl,ore)CO2C14 flCO2CH2phenyl; R3 is a) halo, b) alkyl, c) Cl4 alkoxy, d) benzyl, e)CN, f)SO2F, g)SO2NH2, h)CF3, i)NO2, j)OCH2O, alkyl),k)CO2(C14 1)C (=O) Cl4 alkyl, m)C (=O) NH2, alkyl),orn)NHCO2(C14 o)C (=O)OC (=O) ; Mis a)CN, b) halo, alkyl,c)CO2C14 d)CH (phenyl) 2, Wis a)OR4, b)SR4, c)NER6, or d)NR6R7; R4 is a) alkyl, b) orcycloalkyl, c) aryl; Rugis a) alkyl, cycloalkyl,b)C37 c) aryl, or d)C (=O) Cl4 alkyl; Rg and R7 are independently a) Cl4 alkyl, or b) Rg and R7 together with nitrogen form a 4to 6membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur; Rx is alkyl,a)C118 b) alkenyl, c) Cig alkynyl, d) C24 alkyl substituted with one to three halo, Cl4 alkoxy,OH,SH, orCO2H, e) C24 alkenyl substituted with aryl, wherein the aryl may be in turn substituted with one to three R2, f) (CH2)i aryl, wherein aryl may be substituted with one to three R3, g) (CH2) iQ, wherein het may be substituted with one to three R3, or h) (CH2)iU, wherein Q may be substituted with one to threeR3; aryl is phenyl or naphthyl; het is 5to 10membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur; U is 5to 9membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur; Q is 5or 6membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein nitrogen atom may be in turn substituted with C.

alkyl, phenyl, benzyl,C (=O) C14 alkyl, orCO2C14 alkyl; h is 0,1, or 2; i is 0,1,2,3, or 4; j is 2,3, or 4; k is 0,1,2,3,4,5, or 6; and with the following provisos: a) where Rg is phenyl or 4methoxyphenyl, Rl is other than phenyl, 4methoxyphenyl, or 4chlorophenyl; b) where R 3 isCH2phenyl, R1 is other than phenyl orCH2phenyl; c) where % is H, substituted or unsubstituted alkyl or phenyl, Ri is other than unsubstituted alkyl or phenyl.

3.	A compound of claim 1 wherein X is a)O, or b)NR2; R2 is a) H, alkyl,orb)CO2C14 c)CO2CH2 phenyl.

A compound of claim 1 wherein Ri is a) alkyl, cycloalkyl,b)(CH2)iC37 c) 6,6dimethylbicyclo [3.1. 1]2heptyl, d)(CH2)jM, e)(CH2) jW, f)(CH2) k aryl,(CH2) k aryl, wherein aryl may be substituted with one to three Rg, g) khet, wherein het may be substituted with one to three Rg, h) (CHQ, wherein Q may be substituted with one to three R3, or wherein M, aryl, Rs, i, j, and k are the same as defined in claim 1; Wis a)OR4, b)SR4, c)NHR6, or d); R4 and R, are the same as defined in claim 1; R7areindependentlyR6and a) methyl, or b) R, and R7 together with nitrogen form azetidinyl, pyrrolidinyl, piperdinyl, piperazinyl, 4methyl1piperazinyl, hydantoin, 4 morpholinyl, thiomorpholinyl, or 2oxo1pyrrolidinyl; het is a) furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl; pyrimidinyl,pyridazinyl,pyrazinyl,pyranyl;b)pyridyl, c) indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl; benzothiazole, benzoisoxazole, benzothienyl, indolyl, isoindolyl; or d) quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl or cinnolinyl; and Q is a) 2, 3, or 4piperidinyl, b) 1, or 2pyrrolidinyl, wherein the nitrogen atom in a) and b) may be substituted with Cl4 alkyl, phenyl, benzyl, orC (=O) Cl4 alkyl, c) morpholinyl, d) thiomorpholinyl, e) dioxolanyl, f) imidazolidinyl, g) oxathiolanyl, h) oxazolidinyl, i) tetrahydrofuryl, or j) 2oxolpyrrolidinyl.

5.	A compound of claim 3 wherein het is furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, isoxazolyl, pyridyl, benzothienyl, or indolyl.

6.	A compound of claim 3 wherein Q is 1methyl2pyrrolidinyl, 1methyl4 piperidinyl, 1ethylcarboxylate4piperidinyl, 1benzyl4piperidinyl, or tetrahydrofuryl.

7.	A compound of claim 1 wherein R, is a) chloro, b) fluoro, c) methyl, d) methoxy, e) ethoxy, <BR> <BR> <BR> f)CN,<BR> <BR> <BR> <BR> <BR> 9)SO2N,<BR> <BR> <BR> <BR> <BR> h)NO2, i)OCH2O, or j)C (=O)OC (=O).

A compound of claim 1 wherein Rx is a) Cz8 alkenyl, b) C24 alkyi substituted with halo, orCO2H, c) C2. alkenyl substituted with aryl, wherein the aryl may be in turn substituted with one to three halo, d) (CH2)i aryl, wherein aryl may be substituted with one to three Rg, or e)(CH2) iU,(CH2) iU, wherein het may be substituted with one to three R ; aryl and i are the same as defined in claim 1; R3 is the same as defined in claim 6; and Uis a) furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl; b) pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl or pyranyl; or c) indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl or isoindolyl.

A compound of claim 1 which is 1. tertbutyl4 (5amino1,3,4thiadiazol2yl) tetrahydro1 (2H) pyrazinecarboxylate, 2. N (5amino1,3,4thiadiazol2yl)Nphenethylamine, N (5amino1,3,4thiadiazol2yl)Nbutylamine, 4thiadiazol2ylamine, 4. tertButyl N12 [ (5amino1,3,4thiadiazol2yl) amino] ethyl} carbamate, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] pentanamide, 4thiadiazol2yl]benzamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] benzamide, 11. (E)3 (2chlorophenyl)N [5 (phenethylamino)1,3,4thiadiazol2yl]2 propenamide, thiadiazol2yl]1naphthamide, 13. (E)N [5 (phenethylamino)1,3,4thiadiazol2yl]9octadecenamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] benzamide, 16. (E)N [5 (phenethylamino)1,3,4thiadiazol2yl]3phenyl2propenamide, 4thiadiazol2yl] benzamide, 3, 4thiadiazol2yl]1, 3dihydro2 benzofuran5carboxamide, 19. 4({[5(phenethylamino)1,3,4thiadiazol2yl]amino} carbonyl) benzenesulfonyl fluoride, 4thiadiazol2yl]2furamide, 21. (E)3(2chlorophenyl)N{5[(2furylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 22.2ethoxyN {5[(2furylmethyl) amino]1, 3,4thiadiazol2yl}1naphthamide, 23. (E)N{5[(2furylmethyl)amino]1, 3,4thiadiazol2yl}9octadecenamide, 24.2,6dicEloroN {5[(2furylmethyl) amino]1, 3, 4thiadiazol2yl}benzamide, 25.3,4dichloroN {5[(2furylmethyl) amino]1, 3, 4thiadiazol2yl}benzamide, 26. N {5[(2furylmethyl) amino]1, 3,4thiadiazol2yl}4iodobenzamide, 27. N15 [ (2furyhnethyl) aminol1,3,4thiadiazol2yl}2,4,6triisopropylbenzamide, 28. N {5[(2furylmethyl) amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 29.2, 4difluoroN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 30. 4bromoN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 31. 4methylN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 32. 5chloroN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl)pentanamide, 33. 4cyanoN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 34. 3nitroN(5{[3(2oxo1pyrrlidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 35.3, 5difluoroN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 36. (E)3 (2chlorophenyl)N (5 [ [3 (2oxolpyrrohdinyl) propyllamino)1,3,4 thiadiazol2yl)2propenamide, 37.3, 4dichloroN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 38. (E)N(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2yl)3phenyl 2propenamide, 39. 4iodoN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 40.1, 3dioxoN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2yl)1,3 dihydro2benzofuran5carboxamide, 41. 4{[(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2 yl) amino] carbonyl} benzenesulfonyl fluoride, 42.2,4, 6triisopropylN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol 2yl) benzamide, 43. 5nitroN(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2yl)2 furamide, 44. N(5{[3(2oxo1pyrrolidinyl)propyl]amino}1, 3,4thiadiazol2yl)1 benzothiophene2carboxamide, 45. (E)3(2chlorophenyl)N{5[(2pyridinylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 46. 2ethoxyN{5[(2pyridinylmethyl)amino]1,3,4thiadiazol2yl}1naphthamide, 47. (E)N{5[(2pyridinylmethyl) amino]1,3, 4thiadiazol2yl}9octadecenamide, 48.2,6dichloroN {5[(2pyridinylmethyl) amino]1, 3,4thiadiazol2yl} benzamide, 49. (E)3phenylN{5[(2pyridinylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 50. N{5[(2anilinoethyl)amino]1, 3,4thiadiazol2yl}2methoxybenzamide, 51. N{5[(2anilinoethyl)amino]1, 3,4thiadiazol2yl}4bromobenzamide, 52. N{5[(2anilinoethyl)amino]1,3,4thiadiazol2yl}4methylbenzamide, 53. N{5[(2anilinoethyl)amino]1, 3,4thiadiazol2yl}3nitrobenzamide, 54. (E)N{5[(2anilinoethyl) amino]1,3, 4thiadiazol2yl}3(2chlorophenyl)2 propenamide, 55. N {5[(2anilinoethyl) amino]1, 3,4thiadiazol2yl}2ethoxy1naphthamide, 56. (E)N{5[(2anilinoethyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 57. N{5[(2anilinoethyl)amino]1, 58. N {5[(2anilinoethyl) amino]1, 3,4thiadiazol2yl}3,4dichlorobenzamide, 59. (E)N{5[(2anilinoethyl) amino]1,3,4thiadiazol2yl}3phenyl2propenamide, 60. N {5[(2anilinoethyl) amino]1, 3,4thiadiazol2yl}4iodobenzamide, 61. N{5[(2anilinoethyl)amino]1,3,4thiadiazol2yl}1,3dioxo1,3dihydro2 benzofuran5carboxamide, 62. 4[({5[(2anilinoethyl)amino]1, 3,4thiadiazol2yl} amino) carbonyl] benzenesulfonyl fluoride, 63. N {5[(2anilinoethyl) amino]1, 6triisopropylbenzamide, 64. N {5[(2anilinoethyl) amino]1, 3,4thiadiazol2yl}5nitro2furamide, 65. N {5[(2anilinoethyl) amino]1, 3, 4thiadiazol2yl}1benzothiophene2 carboxamide, 66. N (5{[2(lHindol3yl) ethyl] amino}1, 3,4thiadiazol2yl)2 methoxybenzamide, 67.4bromoN (5{[2(lHindol3yl) ethyl] amino}1, 3,4thiadiazol2yl) benzamide, 68.5chloroN (5{[2(lHindol3yl) ethyl] amino}1, 3,4thiadiazol2yl) pentanamide, 69.4cyanoN (5{[2(lHindol3yl) ethyl] nmino}1, 3,4thiadiazol2yl) benzamide, 70. N (5{[2(lHindol3yl) ethyl] amino}1, 3,4thiadiazol2yl)3nitrobenzamide, 71.3,5difluoroN (5{[2(lHindol3yl) ethyl] nmino}1, 3,4thiadiazol2 yl) benzamide, 72. (E)3(2chlorophenyl)N(5{[2(lHindol3yl) ethyl] amino}1,3,4thiadiazol2 yl)2propenamide, 73.2ethoxyN (5{[2(lHindol3yl) ethyl] amino}1, 3,4thiadiazol2yl)1 naphthamide, 74. (E)N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)9 octadecenamide, 75.2, 6dichloroN(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2 yl) benzamide, 76.3, 4dichloroN(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2 yl) benzamide, 77. N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)4 (trifluoromethyl) benzamide, 78. (E)N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)3phenyl2 propenamide, 79. N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)4iodobenzamide, 80. N(5{[2(1Hindol3yl)ethyl]amino}1,3,4thiadiazol2yl)1,3dioxo1,3dihydro2 benzofuran5carboxamide, 81. 4(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl) amino] carbonyl} benzenesulfonyl fluoride, 82. N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)2,4,6 triisopropylbenzamide, 83. N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)5nitro2furamide, 84. N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)1benzothiophene2 carboxamide, 85. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]2methoxybenzamide, 86. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]4methylbenzamide, 4thiadiazol2yl] pentanamide, 4thiadiazol2yl] benzamide, 89. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]3nitrobenzamide, 90. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]3,5difluorobenzamide, 91. (E)3 (2chlorophenyl)N [5 (cycloheptylamino)1,3,4thiadiazol2yl]2 propenamide, 92. N [5 (cycloheptylamino)1,3, 4thiadiazol2yl]2ethoxy1naphthamide, 93. (E)N [5 (cycloheptylamino)1,3,4thiadiazol2yl]9octadecenamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] benzamide, 96. (E)N [5 (cycloheptylamino)1,3,4thiadiazol2yl]3phenyl2propenamide, 97. N [5 (cycloheptylamino)1,3, 4thiadiazol2yl]4iodobenzamide, 98. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]1,3dioxol, 3dihydro2 benzofuran5carboxamide, 99.4 ({[5(cycloheptylAmino)1, 3,4thiadiazol2yl] amino} carbonyl) benzenesulfonyl fluoride, 100. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]2,4,6triisopropylbenzamide, 101. N [5 (cycloheptylamino)1,3,4thiadiazol2yl]5nitro2furamide, 102. N [5 (cycloheptylamino)1,3, 4thiadiazol2yl]1benzothiophene2 carboxamide, 103. N(5[(cyclohexylmethyl)amino]1, 104. N(5[(cyclohexylmethyl)amino]1,3,4thiadiazol2yl}2methoxybenzamide, 105. N[5[(cycohexylmethyl)amino]1, 3,4thiadiazol2yl}4methylbenzamide, 106.5chloroN {5[(cyclohexylmethyl) amino]1, 3,4thiadiazol2yl} pentanamide, 107.4cyanoN {5[(cyclohexylmethyl) amino]1, 3,4thiadiazol2yl} benzamide, 108. (E)3(2chlorophenyl)N{5[(cyclohexylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 109. N {5[(cyclohexylmethyl) amino]1, 3,4thiadiazol2yl}2ethoxy1naphthamide, 110. (E)N(5[(cyclohexylmethyl)amino]1,3,4thiadiazol2yl}9octadecenamide, 111.3, 4dichloroN{5[(cyclohexymethyl)amino]1, 3,4thiadiazol2yl} benzamide, 112. (E)N(5[(cyclohexylmethyl)maino]1, 3,4thiadiazol2yl}3phenyl2 propenamide, 113. N(5[(cyclohexylmethyl)amino]1,3,4thiadiazol2yl}1,3dioxo1,3dihydro2 benzofuran5carboxamide, 114. N{5[(cyclohexylmethyl)amino]1, 6triisopropyl benzamide, 115. N{5[(cyclohexylmethyl)amino]1, 3,4thiadiazol2yl}5nitro2furamide, 116. N[5({[(2R)6,6dimethylbicyclo[3.1.1]hept2yl]methyl}amino)1,3,4thiadiazol 2yl]2methoxybenzamide, thiadiazol2yl]pentanamide, 118. 4cyanoN[5({[(2R)6,6dimethylbicyclo [3.1. l] hept2yl] methyl} amino)1,3,4 thiadiazol2yl] benzamide, 119. N[5({[(2R)6,6dimethylbicyclo 4thiadiazol 2yl]3,5difluorobenzamide, 120. (E)3(2chlorophenyl)NN[5({[(2R)6,6dimethylbicyclo [3.1.1] hept2 yl] methyl} amino)1,3,4thiadiazol2yl]2propenamide, 121. N [5 ( { [ (2R)6,6dimethylbicyclo [3.1. 1]hept2yl]methyl}amino)1, 3,4thiadiazol 2yl]2ethoxy1naphthamide, 122. (E)N[5({[(2R)6,6dimethylbicyclo [3.1. l] hept2yl] methyl} amino)1,3,4 thiadiazol2yl]9octadecenamide, 123. N [5({[(2R)6 6dimethylbicyclo [3.1. 1]hept2yl]methyl}amino)1, 3,4thiadiazol 2yl]1,3dioxo1,3dihydro2benzofuran5carboxamide, 124. N[5({[(2R)6, 6dimethylbicyclo [3.1. 1]hept2yl]methyl}amino)1, 3,4thiadiazol 2yl]2,4,6triisopropylbenzamide, 125. N[5({[(2R)6,6dimethylbicyclo[3.1.1]hept2yl]methyl}amino)1,3,4thiadiazol 2yl]5nitro2furamide, 126. N[5({[(2R)6,6dimethylbicyclo[3.1.1]hept2yl]methyl}amino)1,3,4thiadiazol 2yl]1benzothiophene2carboxamide, 127. (E)3(2chlorophenyl)N(5{[2(1pyrrolidinyl) ethyl] amino}1,3,4thiadiazol2 yl)2propenamide, 128. (E)N(5{[2(1pyrrolidinyl)ethyl]amino}1, 3,4thiadiazol2yl)9 octadecenamide, 129.2,6dichloroN (5{[2(1pyrrolidinyl) ethyl] amino}1, 3,4thiadiazol2 yl) benzamide, 130. (E)3phenylN(5{[2(1pyrrolidinyl)ethyl]amino}1, 3,4thiadiazol2yl)2 propenamide, 131.2,4, 6triisopropylN(5{[2(1pyrrolidinyl)ethyl]amino}1, 3,4thiadiazol2 yl) benzamide, 132.2ethoxyN {5[(tetrahydro2furanylmethyl) amino]1, 3,4thiadiazol2yl}1 naphthamide, 133. (E)N{5[(tetrahydro2furanylmethyl) amino]1,3,4thiadiazol2yl}9 octadecenamide, 134. N {5[(tetrahydro2furanylmethyl) amino]1, 3, 4thiadiazol2yl}1 benzothiophene2carboxamide, 135. (E)3 (2chlorophenyl)N {5 [ (4pyridinylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 136.2, 6dichloroN{5[(4pyridinylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 137.3, 6dichloroN{5[(4pyridinylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 138. (E)3phenylN {5 [ (4pyridinylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 139. 4iodoN{5[(4pyridinylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, benzofuran5carboxamide, 4thiadiazol2 yl}benzamide, 142. N{5[(4pyridinylmethyl)amino]1,3,4thiadiazol2yl}1benzothiophene2 carboxamide, 143. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}2,4 difluorobenzamide, 144. N{5[(1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}2 methoxybenzamide, 145. N{5[(1,3benzodioxol5ylmethyl)amino]1,3,4thiadiazol2yl}4 bromobenzamide, 146. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}4 methylbenzamide, 147. N{5[(1,3benzodioxol5ylmethyl)amino]1, 3,4thiadiazol2yl}5 chloropentanamide, 148. N{5[(1,3benzodioxol5ylmethyl)amino]1,3,4tghiadiazol2yl}4 cyanobenzamide, 149. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}3,5 difluorobenzamide, 150. (E)N {5 [ (1,3benzodioxol5ylmethyl) amino]1, 3,4thiadiazol2yl}3 (2 chlorophenyl)2propenamide, 151. N {5 [ (1,3benzodioxol5ylmethyl) amino]1, 3,4thiadiazol2yl}2ethoxy1 naphthamide, 152. (E)N {5 [ (1,3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}9 octadecenamide, 153. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}2,6 dichlorobenzamide, 154. (E)N{5[(1,3benzodioxol5ylmethhl)amino]1, 3,4thiadiazol2yl}3phenyl2 propenamide, 155. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}4iodobenzamide, 156. N 5 [ (1, 3benzodioxol5ylmethyl) amino]1,3, 4thiadiazol2yl}1,3dioxo1, 3 dihydro2benzofuran5carboxamide, 157. N{5[(1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}2,4,6 triisopropylbenzamide, 158. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}1 benzothiophene2carboxamide, 159.4cyanoN {5[(2morpholinoethyl) amino]1, 3,4thiadiazol2yl} benzamide, 160. N {5[(2morpholinoethyl) amino]1, 3,4thiadiazol2yl}3nitrobenzamide, 161. (E)N{5[(2morpholinoethyl) amino]1,3,4thiadiazol2yl}3phenyl2 propenamide, 162. N {5[(2morpholinoethyl) amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 163.2,4difluoroN {5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 164. 2methoxyN{5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 165.4methylN {5[(1naphthylmethyl) amino]1, 3,4thiadiazol2yl} benzamide, 166. 5chloroN{5[(1naphthylmethyl)amino]1,3,4thiadiazol2yl}pentanamide, 167. 4cyanoN{5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 168. N {5 [(1naphthylmethyl)amino]1, 3,4thiadiazol2yl}3nitrobenzamide, 169.3, 5difluoroN{5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 170. (E)3(2chlorophenyl)N{5[(1naphthylmethyl) amino]1,3, 4thiadiazol2yl}2 propenamide, 171. 2ethoxyn{5[(1naphthylmethyl)amino]1,3,4thiadiazol2yl}1naphthamide, 172. (E)N {5 [ (1naphthylmethyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 173.2,6dichloroN {5[(1naphthylmethyl) amino]1, 3,4thiadiazol2yl} benzamide, 174. (E)N{5[(1naphthylmethyl)amino1, 3,4thiadiazol2yl}3phenyl2 propenamide, 175. 4iodoN{5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 176. N {5 [ (1naphthylmethyl) amino]1, 3, 4thiadiazol2yl}1, 3dioxol, 3dihydro2 benzofuran5carboxamide, 177. 4[({5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl} amino) carbonyl] benzenesulfonyl fluoride, 178.2,4, 6triisporpylN{5[(1naphthylmethyl)amino]1, 3,4thiadiazol2 yl} benzamide, 179. N {5 [ (1naphthylmethyl) amino]1, 3, 4thiadiazol2yl}5nitro2furamide, 180. NN{5[(1naphthylmethyl)amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 181. N\ (u) 2\ (d)(1naphthylmethyhl)1, 3,4thiadiazole2,5diamine, 182. 2,4difluoroN{5[(4fluorobenzyl)amino]1,3,4thiadiazol2yl}benzamide, 183. N 5 [ (4fluorobenzyl) amino]1,3,4thiadiazol2yl}2methoxybenzamide, 184. 5chloroN{5[(4fluorobenzyl)amino]1, 3,4thiadiazol2yl} pentanamide, 4thiadiazol2yl} benzamide, 186. N{5[(4fluorobenzyl)amino]1, 3,4thiadiazol2yl}3nitrobenzamide, 187.3, 5difluoroN{5[(4fluorobenzyl)amino]1, 3,4thiadiazol2yl} benzamide, 188. (E)3 (2chlorophenyl)N 5 [ (4fluorobenzyl) amino]1,3,4thiadiazol2yl}2 propenamide, 4thiadiazol2yl}1naphthamide, 190. (E)N{5[(4fluorobenzyl)amino]1, 3,4thiadiazol2yl}9octadecenamide, 191.2,6dichloroN {5[(4fluorobenzyl) amino]1, 3,4thiadiazol2yl} benzamide, 192. (E)N{5[(4fluorobenzyl)amino]1,3,4thiadiazol2yl}3phenyl2propenamide, 193. N 5 [ (4fluorobenzyl) amino]1,3,4thiadiazol2yl}1,3dioxo1,3dihydro2 benzofuran5carboxamide, 194. N{5[(4fluorobenzyl}amino]1, 6triisopropylbenzamide, 195. N{5[(4fluorobenzyl)amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 196. 2ethoxyN{5[(3pyridinylmethyl)amino]1,3,4thiadiazol2yl}1naphthamide, 197. (E)N {5 [ (3pyridinylmethyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 198.2, 6dichloroN{5[(3pyridinylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 4thiadiazol2yl} benzamide, 200. (E)3phenylN {5 [ (3pyridinylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 201.2,4, 6triisporpylN{5[(3pyridinylmethyl)amino]1, 3,4thiadiazol2 yl} benzamide, 202. N{5[(3pyridinylmethyl)amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 203.2,4,6triisopropylN {5[(2piperidinoethyl) amino]1, 3,4thiadiazol2 yl} benzamide, 204. (E)N{5[(2ethylhexyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 205.2,6dichloroN {5[(2ethylhexyl) amino]1, 3,4thiadiazol2yl} benzamide, 206.3,4dichloroN {5[(2ethylhexyl) amino]1, 3,4thiadiazol2yl} benzamide, 207. N{5[(2ethylhexyl)amino]1, 3dihydro2 benzofuran5carboxamide, 208. N(5{[4(aminosulfonyl)phenylethyl]amino}1, 3,4thiadiazol2yl)2 methoxybenzamide, 209. N (5 [ [4 (aminosulfonyl) phenethyllaminol1,3,4thiadiazol2yl)4 bromobenzamide, 210. N (5 [ [4 (aminosulfonyl) phenethyllamino)1,3,4thiadiazol2yl)4 methylbenzamide, 211. N(5{[4(aminosulfonyl)phenethyl]amino}1, 3,4thiadiazol2yl)5 chloropentanamide, 212. N (5{[4(aminosulfonyl) phenethyl] nmino}1, 3,4thiadiazol2yl)4 cyanobenzamide, 213. (E)N(5{[4(aminosulfonyl) phenethyl] amino}1,3,4thiadiazol2yl)3 (2 chlorophenyl)2propenamide, 214. N (5{[4(aminosulfonyl) phenethyl] amino}1, 3,4thiadiazol2yl)2ethoxy1 naphthamide, 215. (E)N(5{[4(aminosulfonyl) phenethyl] amino}1,3,4thiadiazol2yl)9 octadecenamide, 216. N (5{[4(aminosulfonyl) phenethyl] nmino}1, 3,4thiadiazol2yl)2,6 dichlorobenzamide, 217. N(5{[4(aminosulfonyl)phenethyl]amino}1, 3,4thiadiazol2yl)3,4 dichlorobenzamide, 218. N(5{[4(aminosulfonyl)phenethyl]amino}1, 3,4thiadiazol2yl)4 (trifluoromethyl) benzamide, 219. (E)N(5{[4(aminosulfonyl)phenyl]amino}1, 3,4thiadiazol2yl)3phenyl2 propenamide, 220. N (5 [ [4 (aminosulfonyl) phenethyllaminol1,3,4thiadiazol2yl)4iodobenzamide, 221. N(5{[4(aminosulfonyl)phenyl]amino}1, 3 dihydro2benzofuran5carboxamide, 222. N(5{[4(aminosulfonyl)phenethyl]amino}1, 3,4thiadiazol2yl)2,4,6 triisopropylbenzamide, 223. N(5{[4(aminosulfonyl)phenyl]amino}1, 3,4thiadiazol2yl)1 benzothiophene2carboxamide, 224. N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)2,4 difluorobenzamide, 225. N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)2 methoxybenzamide, 226.4bromoN (5{[3(cyclohexylamino) propyl] amino}1, 3,4thiadiazol2 yl) benzamide, 227. N (5 { [3 (cyclohexylamino) propyllaminol1,3,4thiadiazol2yl)4 methylbenzamide, 228. 4cyanoN(5{[3(cyclohexylamin)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 229. N (5 { [3 (cydohexylamino) propyl] amino}1, 3,4thiadiazol2yl)3nitrobenzamide, 230. N (5{[3(cyclohexylamino) propyl] amino}1, 3,4thiadiazol2yl)3,5 difluorobenzamide, 231. (E)3(2chlorophenyl)N(5{[3(cyclohexylamino)propyl]amino}1,3,4 thiadiazol2yl)2propenamide, 232. N (51 [3 (cydohexylamino) propyllaminol1,3,4thiadiazol2yl)2ethoxy1 naphthamide, 233. (E)N(5{[3(cyclohexylamino)propyl]amino}1 3,4thiadiazol2yl)9 octadecenamide, 234.2, 6dichloroN(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 235.3, 4dichloroN(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 236. N (5 { [3 (cyclohexylamino) propyllaminol1,3,4thiadiazol2yl)4 (trifluoromethyl) benzamide, 237. (E)N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)3phenyl2 propenamide, 238. N (5 { [3 (cyclohexylamino) propyllaminol1,3,4thiadiazol2yl)4iodobenzamide, 239. N(5{[3(cyclohexylamino)propyl]amino}1, 3 dihydro2benzofuran5carboxamide, 240. 4{[(5(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl) amino] carbonyl}benzenesulfonylfluoride, 241. N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)2,4,6 triisopropylbenzamide, 242. N (5 { [3 (cyclohexylamino) propyllaminol1,3,4thiadiazol2yl)5nitro2 furamide, 243. N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)1 benzothiophene2carboxamide, 244. N(5[(3,4dichlorobenzyl)amino}1, 245. N {5 [ (3,4dichlorobenzyl) amino]1,3,4thiadiazol2yl}2methoxybenzamide, amino]1, 3,4thiadiazol2yl} benzamide, 247. N{5[(3,4dichlorobenzyl)amino]1,3,4thiadiazol2yl}3nitrobenzamide, 247. N{5[(3,4dichlorobenzyl)amino]1,3,4thiadiazol2yl}2enthoxy1naphthamide, 249. (E)N{5[(3,4dichlorobenzyl)amino]1,3,4thiadiazol2yl}9octadecenamide, 250. 2,6dichloroN{5[(3,4dichlorobenzyl)amino]1,3,4thiadiazol2yl}benzamide, 251. (E)N {5 [ (3,4dichlorobenzyl) amino]1, 3,4thiadiazol2yl}3phenyl2 propenamide, 252. N {5 [ (3,4dichlorobenzyl) amino]1,3, 4thiadiazol2yl}1, 3dioxo1,3dihydro2 benzofuran5carboxamide, 253. N {5 [ (3,4dichlorobenzyl) amino]1, 3,4thiadiazol2yl}5nitro2furamide, 4thiadiazol2yl} benzamide, 255. N{5[(3,4dimethoxybenzyl)amino]1,3,4thiadiazol2yl}3nitrobenzamide, 256. N {5 [ (3,4dimethoxybenzyl) amino]1, 3,4thiadiazol2yl}2ethoxy1 naphthamide, 257. (E)N {5 [ (3,4dimethoxybenzyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 258.2, 6dichloroN{5[(3,4dimethoxybenzyl)amino]1, 3,4thiadiazol2 yl} benzamide, 259. N {5 [ (3, 4dimethoxybenzyl) amino]1,3,4thiadiazol2yl}4iodobenzamide, 260. N {5[(3, 4dimethoxybenzyl) amino]1, 3, 4thiadiazol2yl}1,3dioxo1, 3dihydro 2benzofuran5carboxamide, 261. 2,4difluoroN{5[(4phenylbutyl)amino]1,3,4thiadiazol2yl}benzamide, 262. 2methoxyN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} benzamide, 263. 4bromoN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} benzamide, 4thiadiazol2yl} benzamide, 265. 5chloroN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} pentanamide, 266.4cyanoN {5[(4phenylbutyl) amino]1, 3, 4thiadiazol2yl}benzamide, 267. 3nitroN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} benzamide, 268.3, 5difluoroN{5[(4phenylbutyl)amino]1 3,4thiadiazol2yl} benzamide, 269. (E)3(2chlorophenyl)N{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl}2 propenamide, 4thiadiazol2yl}1naphthamide, 271. (E)N {5 [ (4phenylbutyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 272.2, 6dichloroN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} benzamide, 273.3, 4dichloroN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} benzamide, 274. N{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl}4 (trifluoromethyl) benzamide, 275. (E)3phenylN {5 [ (4phenylbutyl) amino]1,3,4thiadiazol2yl}2propenamide, 4thiadiazol2yl} benzamide, 277. 1,3dioxoN{5[(4phenylbutyl)amino]1,3,4thiadiazol2yl}1,3dihydro2 benzofuran5carboxamide, 4thiadiazol2yl} amino) carbonyl] benzenesulfonyl fluoride, 279. 2,4,6triisopropylN{5[(4phenylbutyl)amino]1,3,4thiadiazol2yl}benzamide, 280. 5nitroN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl}2furamide, 281. N {5 [ (4phenylbutyl) amino]1,3,4thiadiazol2yl}1benzothiophene2 carboxamide, 282. N{5[(4diphenylethyl)amino]1,3,4thiadiazol2yl}2,4difluorobenzamide, 283. Nf5 [ (2,2diphenylethyl) amino]1, 3,4thiadiazol2yl}2methoxybenzamide, amino]1, 3,4thiadiazol2yl} benzamide, 285. 5chloroN{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}pentanamide, 286. 4cyanoN{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}benzamide, 287. Nf5 [ (2,2diphenylethyl) amino]1,3,4thiadiazol2yl}3,5difluorobenzamide, 288. (E)3(2chlorophenyl)N{5[(2, 2diphenylethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 289. N {5[(2,2diphenylethyl) amino]1,3, 4thiadiazol2yl}2ethoxy1napthamide, 290. (E)N{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}9octadecenamide, 291. 2,6dichloroN{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}pentanamide, 292. N{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}1,3dioxo1,3dihydro2 benzofuran5carboxamide, amino]1, 3,4thiadiazol2yl} amino) carbonyl] benzenesulfonyl fluoride, 294. N{5[(2, 2diphenylethyl) amino]1, 6triisopropyl benzamide, 295. Nf5 [ (2,2diphenylethyl) amino]1, 3,4thiadiazol2yl}5nitro2furamide, 296. N{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}benzothiophene2 carboxamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yllpentanamide, 4thiadiazol2yl] benzamide, 302. 3nitroN[5(undecylamino)1,3,4thiadiazol2yl]benzamide, 4thiadiazol2yl]benzamide, 304. (E)3 (2chlorophenyl)N [5 (undecylamino)1,3,4thiadiazol2yl]2 propenamide, 4thiadiazol2yl]1naphthamide, 306. (E)N [5 (undecylamino)1,3,4thiadiazol2yl]9octadecenamide, 4thiadiazol2yl] benzamide, 4thiadiazol2yl]benzamide, 4thiadiazol2yl]benzamide, 310. (E)3phenylN [5 (undecylamino)1,3,4thiadiazol2yl]2propenamide, 4thiadiazol2yl]benzamide, 312. 1,3dioxoN[5(undecylamino)1,3,4thiadiazol2yl]1,3dihydor2benzofuran 5carboxamide, 313. 4({[5(undecylamino)1, 3,4thiadiazol2yl] amino} carbonyl) benzenesulfonyl fluoride, 4thiadiazol2yl] benzamide, 4thiadiazol2yl]2furamide, 316. N [5 (undecylamino)1,3,4thiadiazol2yl]1benzothiophene2carboxamide, 317. N {5 [ (3,3diphenylpropyl) amino]1, 318. N {5 [ (3,3diphenylpropyl) amino]1,3, 4thiadiazol2yl}2methoxybenzamide, 319. 4bromoN{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}benzamide, 320. 5chloroN{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}pentanamide, 321. 4cyanoN{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}benzamide, 322. N{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}3nitrobenzamide, 323. N {5 [ (3,3diphenylpropyl) amino]1, 324. (E)3(2chlorophenyl)N{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl} 2propenamide, 325. N{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}2ethoxy1 naphthamide, 326. (E)N {5 [ (3,3diphenylpropyl) amino]1, 3,4thiadiazol2yl}9octadecenamide, 327.2, 6dichloroN{5[(3,3diphenylpropyl)amino]1, 3,4thiadiazol2yl} benzamide, 328. N {5 [ (3,3diphenylpropyl) amino]1,3, 4thiadiazol2yl}4(trifluoromethyl) benzamide, 329. (E)N{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}3phenyl2 propenamide, 330. N{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}4iodobenzamide, 331. N {5 [ (3,3diphenylpropyl) amino]1,3, 4thiadiazol2yl}1,3dioxo1, 3dihydro2 benzofuran5carboxamide, 332. 4[({5[(3,3diphenylpropyl)amino]1, 3,4thiadiazol2yl} amino) carbonyl] benzenesulfonyl fluoride, 333. N {5 [ (3,3diphenylpropyl) amino]1, 6 triisopropylbenzamide, 334. N{5[(3, 3diphenylpropyl) amino]1,3,4thiadiazol2yl}5nitro2furamide, 335. N {5 [ (3,3diphenylpropyl) amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 336.2, 4difluoroN(5{[2(2thienyl)ethyl]amino}1, 3,4thiadiazol2yl) benzamide, 337.4cyanoN (5{[2(2thienyl) ethyl] amino}1, 3,4thiadiazol2yl) benzamide, 338.3nitroN(5{[2(2thienyl) ethyl] amino}1, 3, 4thiadiazol2yl) benzamide, 339. (E)3(2chlorophenyl)N(5{[2(2thienyl)ethyl]amino}1, 3,4thiadiazol2yl)2 propenamide, 340. 2ethoxyn{5{[2(2thienyl)ethyl]amino}1, 3,4thiadiazol2yl)1naphthamide, 341. (E)N(5{[2(2thienyl) ethyl] amino}1,3,4thiadiazol2yl)9octadecenamide, 342.2, 6dichloroN(5{[2(2thienyl)ethyl]amino}1, 3,4thiadiazol2yl) benzamide, 343. (E)3phenylN(5{[2(2thienyl) ethyl] amino}1,3,4thiadiazol2yl)2 propenamide, 344.4iodoN (5{[2(2thienyl) ethyl] amino}1, 3,4thiadiazol2yl) benzamide, 345.1, 3dioxoN(5{[2(2thienyl)ethyl]amino}1, 3,4thiadiazol2yl)1,3dihydro2 benzofuran5carboxamide, 346.2,4,6triisopropylN (5{[2(2thienyl) ethyl] amino}1, 3,4thiadiazol2 yl) benzamide, 347. N (5{[2(2thienyl) ethyl] amino}1, 3,4thiadiazol2yl)1benzothiophene2 carboxamide, 348. (E)N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)3 (2 chlorophenyl)2propenamide, 349. N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)2ethoxy1 naphthamide, 350. (E)N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)9 octadecenamide, 351. N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)2,6 dichlorobenzamide, 352. n(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)3,4 dichlorobenzamide, 353. N(5{[4(aminosulfonyl)benzyl]amino1, 3,4thiadiazol2yl)4 (trifluoromethyl) benzamide, 354. (E)N(5{[4(aminosulfonyl) benzyl] amino}1,3,4thiadiazol2yl)3phenyl2 propenamide, 355. N(5{[4(aminosulfonyl)benzyl]amino}1,3,4thiadiazol2y)4iodobenzamide, 356. N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)2,4,6 triisopropylbenzamide, 357. N (5 [ [4 (aminosulfonyl) benzyllaminol1,3,4thiadiazol2yl)1benzothiophene 2carboxamide, 358. (E)3(2chlorophenyl)N(5{[3(4methylpiperazino)propyl]amino}1, 3,4 thiadiazol2yl)2propenamide, 359. (E)N(5{[3(4methylpiperazino)propyl]amino}1, 3,4thiadiazol2yl)9 octadecenamide, 4thiadiazol2 yl) benzamide, 361. (E)N{5[(2cyanoethyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 362.2, 6dichloroN{5[(2cyanoethyl)amino]1, 3,4thiadiazol2yl} benzamide, 363. N {5[(2cyanoethyl) amino]1, 6triisopropylbenzamide, 364.2,4difluoroN (5{[2(phenylsulfanyl) ethyl] amino}1, 3,4thiadiazol2 yl) benzamide, 365.4bromoN (5{[2(phenylsulfanyl) ethyl] amino}1, 3,4thiadiazol2yl) benzamide, 366.5chloroN (5{[2(phenylsulfanyl) ethyl] amino}1, 3,4thiadiazol2yl) pentanamide, 367. (E)3(2chlorophenyl)N(5{[2(phenylsulfanyl)ethyl]amino]1, 3,4thiadiazol2 yl)2propenamide, 368.2ethoxyN (5{[2(phenylsulfanyl) ethyl] amino}1, 3,4thiadiazol2yl)1 naphthamide, 369. (E)N(5{[2(phenylsulfanyl)ethyl]amino]1, 3,4thiadiazol2yl)9 octadecenamide, 370. (E)3phenylN(5{[2(phenylsulfanyl) ethyl] amino}1,3,4thiadiazol2yl)2 propenamide, 371. 4iodoN(2{[2(phenylsulfanyl)ethyl]amino]1, 3,4thiadiazol2yl) benzamide, 3,4thiadiazol2yl)1,3dihydro 2benzofuran5carboxamide, 373. 4cyanoN{5[(2thienylmethyl)amino]1, 3,4thiadiazol2yl} benzamide, 374. (E)3(2chlorophenyl)N{5[(2thienylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 375.2ethoxyN {5[(2thienylmethyl) nmino]1, 3, 4thiadiazol2yl}1naphthamide, 376. (E)N{5[(2thienylmethyl) amino]1,3, 4thiadiazol2yl}9octadecenamide, 377.2,6dichloroN {5[(2thienylmethyl) amino]1, 3,4thiadiazol2yl} benzamide, 378.4iodoN {5[(2thienylmethyl) amino]1, 3,4thiadiazol2yl} benzamide, 379. 1,3dioxoN{5[(2thienylmethylamino]1,3,4thiadiazol2yl}1,3dihydro2 benzofuran5carboxamide, 380.2,4,6triisopropylN {5[(2thienylmethyl) amino]1, 3,4thiadiazol2 yl}benzamide, 381. N {5[(2thienylmethyl) amino]1, 3, 4thiadiazol2yl}1benzothiophene2 carboxamide, 382. N (5{[2(acetylamino) ethyl] amino}1, 3, 4thiadiazol2yl)2ethoxy1 naphthamide, 383. (E)N(5{[2(acetylamino)ethyl]amino]1, 3,4thiadiazol2yl)9octadecenamide, 384. (E)N(5{[2(acetylamino)ethyl]amino]1, 3,4thiadiazol2yl)3phenyl2 propenamide, 385. N(5{[2(acetylamino)ethyl]amino]1,3,4thiadiazol2yl)1,3dioxo1,3dihydro 2benzofuran5carboxamide, 386. N(5{[2(acetylamino)ethyl]amino]1, 6 triisopropylbenzamide, 387. N(5{[2(acetylamino)ethyl]amino]1, 3,4thiadiazol2yl)1benzothiophene2 carboxamide, 388.4bromoN (5{[3(lHimidazol1yl) propyl] amino}1, 3,4thiadiazol2 yl) benzamide, 389. (E)3(2chlorophenyl)N(5{[3(1Himidazol1yl)propyl]amino]1, 3,4 thiadiazol2yl)2propenamide, 390.2ethoxyN (5{[3(lHimidazol1yl) propyl] amino}1, 3,4thiadiazol2yl)1 naphthamide, 391. (E)N(5{[3(1Himidazol1yl)propyl]amino]1, 3,4thiadiazol2yl)9 octadecenamide, 392.2,6dichloroN (5{[3(lHimidazol1yl) propyl] amino}1, 3,4thiadiazol2 yl) benzamide, 393.3, 4dichloroN(5{[3(1Himidazol1yl)propyl]amino]1, 3,4thiadiazol2 yl) benzamide, 394. (E)N(5{[3(lHimidazol1yl) propyl] amino}1,3,4thiadiazol2yl)3phenyl2 propenamide, 395. N(5{[3(1Himidazol1yl)propyl]amino]1, 3,4thiadiazol2yl)4iodobenzamide, 396. N (5{[3(lHimidazol1yl) propyl] amino}1, 3,4thiadiazol2yl)2,4,6 triisopropylbenzamide, 397. tertbutyl 3[(5{[(E)3(2chlorophenyl)2propenyl]amino]1, 3,4thiadiazol2 yl)amino]propanoate, 398. tertbutyl 3[(5{[(2ethoxy1naphtyl)carbonyl]amino]1, 3,4thiadiazol2 yl) amino] propanoate, 399. tertbutyl 3({5[(E)9octadeceoylamino]1, 3,4thiadiazol2 yl}amino)propanoate, 400. tertbutyl 3 ({5[(2,6dichlorobenzoyl) amino]1, 3,4thiadiazol2 yl}amino)propanoate, 401. tertbutyl 3 ( {5 [ (3,4dichlorobenzoyl) amino]1,3,4thiadiazol2 yl} amino) propanoate, 402. tertbutyl 3[(5{[49trifluoromethyl)benzoyl]amino]1, 3,4thiadiazol2 yl) amino] propanoate, 403. tertbutyl 3[(5{[(E)3phenyl2propenoyl]amino]1, 3,4thiadiazol2 yl) amino] propanoate, 404. 3[(5{[(1,3dioxo1,3dihydro2benzofuran5yl)carbonyl]amino} 1,3,4thiadiazol2yl)amino]propanoate, 405. 3({5[(2,4,6triisopropylbenzoyl)amino]1,3,4thiadiazol2 yl} amino) propanoate, 406. (E)3 (2chlorophenyl)N [5 (cyclopropylamino)1,3,4thiadiazol2yl]2 propenamide, 407. N [5 (cyclopropylamino)1,3, 4thiadiazol2yl]2ethoxy1naphthamide, 408. (E)N [5 (cydopropylamino)1,3,4thiadiazol2yl]9octadecenamide, 409. (E)N [5 (cyclopropylamino)1,3,4thiadiazol2yl]3phenyl2propenamide, 410. N [5 (cyclopropylamino)1,3, 4thiadiazol2yl]1benzothiophene2 carboxamide, 411. (E)3(2chlorophenyl)N{5[(cyclopropylmethyl) amino]1,3,4thiadiazol2yl}2 propenamide, 412. N{5[(cyclopropylmethyl)amino]1, 3,4thiadiazol2yl}2ethoxy1naphthamide, 413. (E)N{5[(cyclopropylmethyl) amino]1,3, 4thiadiazol2yl}9octadecenamide, 414. N {5[(cyclopropylmethyl) amino]1, 3, 4thiadiazol2yl}4iodobenzamide, 415. (E)3(2chlorophenyl)N(5{[2(lHimidazol4yl) ethyl] amino}1,3,4thiadiazol 2yl)2propenamide, 416.2ethoxyN (51 [2 (lHimidazol4yl) ethyl] amino}1,3,4thiadiazol2yl)1 naphthamide, 417. (E)N(5{[2(lHimidazol4yl) ethyl] amino}1,3,4thiadiazol2yl)9 octadecenamide, 418.2,6dichloroN (5{[2(lHimidazol4yl) ethyllamino}1, 3,4thiadiazol2 yl) benzamide, 419. (E)N(5{[2(lHimidazol4yl) ethyl] amino}1,3,4thiadiazol2yl)3phenyl2 propenamide, 420. N(5{[2(lHimidazol4yl) ethyl] amino}1, 3, 4thiadiazol2yl)4iodobenzamide, 421. N(5{[2(1Himidazol4yl)ethyl]amino]1, 3,4thiadiazol2yl)2,4,6 triisopropylbenzamide, 422. N (5 { [2 (1Himidazol4yl)ethyl]amino]1, 3,4thiadiazol2yl)1 benzothiophene2carboxamide, 423.4bromoN (5{[2(ethylsulfanyl) ethyl] amino}1, 3,4thiadiazol2yl) benzamide, 424. (E)3(2chlorophenyl)N(5{[2(ethylsulfanyl) ethyl] amino}1,3,4thiadiazol2 yl)2propenamide, 425. 2ethoxyN(5{[2(ethylsulfanyl)ethyl]amino]1, 3,4thiadiazol2yl)1 naphthamide, 426. (E)N(5{[2(ethylsulfanyl)ethyl]amino]1, 3,4thiadiazol2yl)9 octadecenamide, 427.2,6dichloroN (5{[2(ethylsulfanyl) ethyl] amino}1, 3,4thiadiazol2 yl) benzamide, 428.3, 4dichloroN(5{[2(ethylsulfanyl)ethyl]amino]1, 3,4thiadiazol2 yl) benzamide, 429. N (5{[2(ethylsulfanyl) ethyl] amino}1, 3,4thiadiazol2yl)4 (trifluoromethyl) benzamide, 430. (E)N(5{[2(ethylsulfanyl) ethyl] amino}1,3,4thiadiazol2yl)3phenyl2 propenamide, 431. N(5{[2(ethylsulfanyl)ethyl]amino]1, 3,4thiadiazol2yl)4iodobenzamide, 432. N(5{[2(ethylsulfanyl)ethyl]amino]1, 3,4thiadiazol2yl)1benzothiophene2 carboxamide, 433. (E)3 (2chlorophenyl)N [5 (cyclobutylamino)1,3,4thiadiazol2yl]2 propenamide, 434. N [5 (cyclobutylamino)1,3, 4thiadiazol2yl]2ethoxy1naphthamide, 435. (E)N [5 (cyclobutylamino)1,3,4thiadiazol2yl]9octadecenamide, 436. (E)N(5{[2(1methyl2pyrrolidinyl) ethyl] amino}1,3,4thiadiazol2yl)9 octadecenamide, 437.2,4, 6triisopropylN(5{[2(1methyl2pyrrolidinyl)ethyl]amino]1, 3,4 thiadiazol2yl) benzamide, 438. N [5 (2, 3dihydrolHinden1ylamino)1,3, 4thiadiazol2yl]3nitrobenzamide, 439. N[5(2,3dihydro1Hindent1ylamino)1,3,4thiadiazol2yl]2ethoxy1 naphthamide, 440. (E)N[5(2,3dihydro1Hindent1ylamino)1, 3,4thiadiazol2yl]9 octadecenamide, 441.2, 6dichloroN[5(2,3dihydro1Hindent1ylamino)1, 3,4thiadiazol2 yl] benzamide, 442. N [5 (2, 3dihydrolHinden1ylamino)1,3, 4thiadiazol2yl]1, 3dioxol, 3 dihydro2benzofuran5carboxamide, 443. N [5 (2, 3dihydrolHinden1ylamino)1,3, 4thiadiazol2yl]5nitro2 furamide, 444. (E)3 (2chlorophenyl)N [5 (neopentylamino)1,3,4thiadiazol2yl]2 propenamide, 4thiadiazol2yl]1naphthamide, 4thiadiazol2yllbenzamide, 4thiadiazol2 yl] benzamide, 4thiadiazol2 yl] benzamide, 449.3, 5difluoroN[5(1, 2,3, 4tetrahydro1naphthalenylamino)1, 3,4thiadiazol2 yl] benzamide, 450. (E)3(2chlorophenyl)N[5(1, 4 thiadiazol2yl]2propenamide, 4thiadiazol2yl] 1naphthamide, 452. (E)N [5 (1,2,3,4tetrahydro1naphthalenylamino)1,3,4thiadiazol2yl]9 octadecenamide, 4thiadiazol2 yl]benzamide, 454. 1,3dioxoN[5(1,2,3,4tetrahydro1naphthalenylamino)1,3,4thiadiazol2yl] 1,3dihydro2benzofuran5carboxamide, 455. 5nitroN[5(1, 4thiadiazol2yl]2 furamide, 456 N[5(1,2,3,4tetrahydro1naphthalenylamino)1,3,4thiadiazol2yl]1 benzothiophene2carboxamide, 457. ethyl 4[(5{[(E)3(2chlorophenyl2propenoyl]amino]1, 3,4thiadiazol2 yl) amino] tetrahydro1 (2H)pyridinecarboxylate, 458. 4[(5{[(2ethoxynaphthyl)carbonyl]amino}1,3,4,triadiazol2 yl)amino]tetrahydro1(2H)pyridinecarboxylate, 459. ethyl 4({5[(E)9octadecenoylamino]1, 3,4thiadiazol2yl} amino) tetrahydro 1 (2H)pyridinecarboxylate, 460. ethyl 4 ({5[(2,6dichlorobenzoyl) amino]1,3,4thiadiazol2yl} amino) tetrahydro 1 (2H)pyridinecarboxylate, 461. ethyl4 ( {5 [ (1benzothiophen2ylcarbonyl) amino]1,3,4thiadiazol2 yl}amino)tetrahydro1(2H)pyridinecarboxylate, 462. N {5 [ (1benzyl4piperidinyl) amino]1,3,4thiadiazol2yl}4bromobenzamide, 463. (E)N{5[(1benzyl4piperidinyl)amino]1, 3,4thiadiazol2yl}3 (2 chlorophenyl)2propenamide, 464. N{5[(1benzyl4piperidinyl)amino]1,3,4thiadiazol2yl}2ethoxy1 naphthamide, 465. (E)N{5[(1benzyl4piperidinyl) amino]1,3, 4thiadizol2yl}9 octadecenamide, 466. N{5[(1benzyl4piperidinyl)amino]1, 3,4thiadiazol2yl}2,6 dichlorobenzamide, 467. (E)N{5[(1benzyl4piperidinyl) amino]1,3,4thiadiazol2yl}3phenyl2 propenamide, 468. N{5[(1benzyl4piperidinyl)amino]1, 3,4thiadiazol2yl}4iodobenzamide, 469. N {5 [ (1benzyl4piperidinyl) amino]1,3, 4thiadizol2yl}1,3dioxo1, 3dihydro2 benzofuran5carboxamide, 4thiadiazol2 yl} amino) carbonyl] benzenesulfonyl fluoride, 471. N {5 [ (1benzyl4piperidinyl) amino]1,3,4thiadiazol2yl}2,4,6 triisopropylbenzamide, 472. N {5 [ (1benzyl4piperidinyl) amino]1,3,4thiadiazol2yl}5nitro2furamide, 473. N{5[(1benzyl4piperidinyl)amino]1, 3,4thiadiazol2yl}1benzothiophene2 carboxamide, 474. (E)N(5{[2(dimethylamino)ethyl]amino]1, 3,4thiadiazol2yl)9 octadecenamide, or 475. N(5{[2(dimethylamino)ethyl]amino]1, 3,4thiadiazol2yl)2,4,6 triispropylbenzamide.

10.

A compound of claim 1 which is 1. N(5{[3(cyclohexlamino)propyl]amino}1, 3,4thiadiazol2yl)2ethoxy1 naphthamide, 2. N(5{[3(cyclohexlamino)propyl]amino}1, 3 dihydro2benzofuran5carboxamide, 3. N {5 [ (3,3diphenylpropyl) amino]1, 3, 4thiadiazol2yl}1, 3dioxol, 3dihydro2 benzofuran5carboxamide, 4. (N{5[(2, 2diphenylethyl) amino]1,3, 4thiadiazol2yl}1, 3dioxol, 3dihydro2 benzofuran5carboxamide, 3, 4thiadiazol2yl]1, 3dihydro2benzofuran 5carboxamide, 6. N [5 ( { [ (2R)6, 6dimethylbicyclo [3.1. 1]hept2yl]methyl}amino)1, 3,4thiadiazol 2yl]1,3dioxo1,3dihydro2benzofuran5carboxamide, 7.1, 3dioxoN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl}1,3dihydro2 benzofuran5carboxamide, 8. N (5 { [2 (lHmdol3yl) ethyl] amino}l, 3, 4thiadiazol2yl)1, 3dioxol, 3dihydro2 benzofuran5carboxamide, 9. (E)N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)9 octadecenamide, 10. 2ethoxyN(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)1 naphthamide, 11.2, 6dichloroN(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2 yl) benzamide, 12. N [5 (cycloheptylamino)1,3, 4thiadiazol2yl]2ethoxy1naphthamide, 13. N[5({[(2R)6,6dimethylbicyclo[3.1.1]hept2yl]methyl}amino)1,3,4thiadiazol 2yl]2ethoxy1naphthamide, 14. (E)N(5{[4(aminosulfonyl) benzyl] amino}1,3,4thiadiazol2yl)9 octadecenamide, 15 N{5[(2,2diphenylethyl)amino]1,3,4thiadiazol2yl}2ethoxy1naphthamide, 16. (E)N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)3phenyl2 propenamide, 17.2, 6dichloroN{5[(3, 3diphenylpropyl) amino]1, 3,4thiadiazol2yl} benzamide, amino]1, 3,4thiadiazol2yl} benzamide, 19. (E)N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}9 octadecenamide, 20. N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)2,6 dichlorobenzamide, 21.2,6dichloroN (5{[2(lHindol3yl) ethyl] amino}1, 3,4thiadiazol2 yl) benzamide, 22. 4cyanoN{5[(2,2diphenylethyl)amino]1, 3,4thiadiazol2yl} benzamide, 23. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3, 4thiadiazol2yl}1, 3dioxol, 3 dihydro2benzofuran5carboxamide, 24. 4cyanoN(5{[3(cyclohexylamino)proyl]amino}1, 3,4thiadiazol2 yl)benzamide, 25. N (5 ( [2 (lHindol3yl) ethyl] amino}1, 3, 4thiadiazol2yl)5nitro2furamide, 26. 2,6dichloroN[5({[(2R)6,6dimethylbicyclo[3.1.1]hept2yl]methyl}amino) 1,3,4thiadiazol2yl]benzamide, 27.4cyanoN (5{[2(lHindol3yl) ethyl] amino}1, 3, 4thiadiazol2yl) benzamide, 28 N [5 (cycloheptylamino)1,3, 4thiadiazol2yl]1, 3dioxol, 3dihydro2 benzofuran5carboxamide, 29. N {5 [ (1, 3benzodioxol5ylmethyl) amino]1,3,4thiadiazol2yl}2,6 dichlorobenzamide, 30. N{5[(2, 2diphenylethyl) amino]1,3,4thiadiazol2yl}2methoxybenzamide, 31. (E)N(5{[4(aminosulfonyl)benzyl]amino}1, 3,4thiadiazol2yl)3phenyl2 propenamide, 32. (E)N[5({[(2R)6,6dimethylbicyclo[3.1.1]hept2yl]methyl}amino)1,3,4 thiadiazol2yl]9octadecenamide, 33. (E)N(5{[2(1Hindol3yl)ethyl]amino}1, 3,4thiadiazol2yl)9 octadecenamide, 34. (E)N [5 (cycloheptylamino)1,3, 4thiadiazol2yl]9octadecenamide, 35. (E)N {5 [ (4fluorobenzyl) amino]1,3,4thiadiazol2yl}9octadecenamide, 36.2, 6dichloroN{5[(4phenylbutyl)amino]1, 3,4thiadiazol2yl} benzamide, or 37. N (5 [ [4 (aminosulfonyl) benzyllamino)1,3,4thiadiazol2yl)2ethoxy1 naphthamide.

11.

A compound of claim 1 which is 1. N(5{[3(cyclohexylamino)propyl]amino}1, 3,4thiadiazol2yl)2ethoxy1 naphthamide, 2. N(5{[3(cyclohexylamino)propyl]amino}1, 3 dihydro2benzofuran5carboxamide, 3. N{5[(3,3diphenylpropyl)amino]1,3,4thiadiazol2yl}1,3dioxo1,3dihydro2 benzofuran5carboxamide, 4. N {5 [ (2,2diphenylethyl) amino]1, 3dihydro2 benzofuran5carboxamide, 5carboxamide, 6. N[5({[(2R)6, 6dimethylbicyclo [3.1. 1]hept2yl]methyl}amino]1, 3,4thiadiazol 2yl]1,3dioxo1,3dihydro2benzofuran5carboxamide, 3,4thiadiazol2yl}1,3dihydro2 benzofuran5carboxamide, 8. N (5{[2(lHindol3yl) ethyllamino}1, 3,4thiadiazol2yl)1,3dioxol, 3dihydro2 benzofuran5carboxamide, or 9. (E)N(5{[3(cyclohexylamino) propyl] amino}1,3,4thiadiazol2yl)9 octadecenamide.

12.	A pharmaceutical composition which comprises an effective amount of the compound of claim 1 to treat cytomegalovirus infection and a pharmaceutically acceptable carrier.

13.	A method for treating viral infections in a mammal comprising administering to said mammal in need thereof an effective amount of a compound of formula I of claim 1.

14.	A method of claim 12 wherein said effective amount of a compound of formula is administered orally, parenterally or topically in a pharmaceutical composition.

15.	A method of claim 12 wherein said viral infection is human cytomegalovirus infection.

16.	A method of claim 12 wherein said effective amount of a compound of formula is administered in an amount of from about 0.1 to 300 mg/kg of mammal body weight.

Description:

1,3,4-THIADIAZOLES USEFUL FOR THE TREATMENT OF CMV INFECTIONS BACKGROUND OF THE INVENTION The present invention relates to novel 1,3,4-thiadiazole derivatives having useful antiviral activity against herpes virus, cytomegalovirus (CMV). The invention also relates to a pharmaceutical composition containing such compounds and methods for the treatment of such viral infections. Many of these compounds are also active against other herpes viruses, such as the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, and the human herpes virus type 8 (HHV-8).

INFORMATION DISCLOSURE Derwent Abstracts 07484C/05 discloses 2-acylamino-1,3,4-thiadiazole derivatives useful as pesticides, optical brightening agents, and intermediates for pharmaceuticals.

Derwent Abstracts 46012X/24 discloses anti-inflammatory composition containing 1,3,4-thiadiazoles derivatives as active agents.

J. Chem. Soc. (C), Vol. 13,1813-1823, (1970) describes addition-cyclisation reactions undergone by aroyl isothiocyanates with NN'-diaminoguanidines.

J. Heterocyclic Chem. Vol. 25,1071-1074 describes a new route to 1,2,4- triazoles and 1,3,4-thiadiazoles from 1-acylbithiourea.

SUMMARY OF THE INVENTION The present invention provides a compound of formula I I or pharmaceutically acceptable salts thereof wherein: Yis a)-NHRl, or X is-O-,-S (=O) h-,-CH2-, or-NR2-;

Ru ils alkyl,a)C1-18 cycloalkyl,b)-(CH2)i-C3-7 c)-(CH2)i-bicycloalkyl, d)-(CH2)j-M, e)-(CH2)j-W, f) -(CH2)k aryl, wherein aryl may be substituted with one to three R3, g) -(CH2) k-het, wherein het may be substituted with one to three R3, h) -(CH2)k-Q, wherein Q may be substituted with one to three R3, or i) H; R2 is a) H, b) Cl. alkyl, c) alkyl, d) alkyl, alkyl,ore)-CO2C1-4 f)-CO2CH2phenyl; Rosis a) halo, b) alkyl, c) Cl. alkoxy, d) benzyl, e)-CN, f)-SO2F, g)-SO2NH2, h)-CF3, i)-NO2, j)-OCH2O-, alkyl),k)-CO2(C1-4 1)-C (=O) Cl alkyl, m)-C (=O) NH2, n)-NHCO2 (Cl4 alkyl), or o)-C (=O)-O-C (=O)- ; M is a)-CN b) halo, alkyl,c)-CO2C1-4 d)-CH (phenyl) 2, Wis a)-OR4, b)-SR4, orc)-NHR5, d) -NR6R7; R4 is a) Cl. 4 Yl b) C37 cycloalkyl, or c) aryl, R6 is a) C14 alkyl, b) C37 cycloalkyl, c) aryl, or d)-C (=O) C1-4 alkyl ; Rg and R7 are independently a) C14 alkyl, or b) Rg and R7 together with nitrogen form a 4-to 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur; Rxis alkyl,a)C1-18 b) alkenyl, c) alkynyl, d) C24 alkyl substituted with one to three halo, C1-3 alkoxy,-OH,-SH, or-CO2H, e) C24 alkenyl substituted with aryl, wherein the aryl may be in turn substituted with one to three R2, f) -(CH2) i aryl, wherein aryl may be substituted with one to three R3, g)-(CH2) i-Q,(CH2) i-Q, wherein het may be substituted with one to three R3, or

h)-(CH2) i-U,(CH2) i-U, wherein Q may be substituted with one to three R3; aryl is phenyl or naphthyl; het is 5-to 10-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur; U is 5-to 9-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur; Q is 5-or 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein nitrogen atom may be in turn substituted with Cl4 alkyl, phenyl, benzyl,-C (=O) Cl4 alkyl, or- CO2C14 alkyl; h is 0,1, or 2; i is 0,1,2,3, or 4; j is 2,3, or 4; k is 0,1,2,3,4,5, or 6; and with the following provisos: a) where Rg is phenyl or 4-methoxyphenyl, Rl is other than phenyl, 4-methoxyphenyl, or 4-chlorophenyl; b) where Rs is-CH2phenyl, Ri is other than phenyl or-CH2phenyl; c) where R3 is H, substituted or unsubstituted alkyl or phenyl, Ri is other than unsubstituted alkyl or phenyl.

The compounds of the present invention have antiviral activity against cytomegalovirus (CMV), a member of herpes virus.

DETAILED DESCRIPTION OF THE INVENTION For the purpose of the present invention, the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i. e., the prefix Ci. defines the number of carbon atoms present from the integer"i"to the integer"j", inclusive.

Thus, Cl, alkyl refers to alkyl of one to four carbon atoms, inclusive, or methyl, ethyl, propyl, butyl, and isomeric forms such as, for example, straight and branched form thereof.

The terms"Cl4 alkyl", and"Cl_l8 alkyl"refer to an alkyl group having one to four, or one to eighteen carbon atoms respectively such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric forms thereof.

The terms"C2-18 alkenyl"refers to at least one double bond alkenyl group having two to eighteen carbon atoms, for example, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, heptdienyl, octenyl, octadienyl, octatrienyl, nonenyl, undecenyl, dodecenyl, etc., and their isomeric forms thereof.

The term"Cg alkynyl"refers to at least one triple bond alkynyl group having two to twelve carbon atoms such as, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, octadiynyl, octatriynyl, nonynyl, nonediynyl, etc., and their isomeric forms thereof.

The term"C3 7 cycloalkyl"refers to monocyclic hydrocarbons having three to seven carbon atoms such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof, preferably an cycloalkyl group having three to six carbon atoms.

The term"bicycloalkyl"refers to saturated alicyclic hydrocarbon systems consisting of two rings only, having two or more atoms in common.

The terms"C14 alkoxy"refers to an alkyl group having one to four carbon atoms attached to an oxygen atom of hydroxyl group such as; for example, methoxy, ethoxy, propyloxy, butyloxy, and their isomeric forms thereof.

The term"aryl"refers to monocarbocyclic or bicarbocyclic aromatic moiety such as; for example phenyl, naphthyl, biphenyl. Each of these moieties may be substituted as appropriate. Aryl is preferably phenyl or phenyl substituted with Cl4 alkyl, C14 alkoxy, halo,-CN,-SO2NH2,-SO2F-,-N02,-C (=O)-O-C (=O)- or -OCH20-.

The term"het"refers to a 5-to 10-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur such as, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl, isoindolyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl or cinnolinyl.

The term"U"refers to 5-to 9-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur such as, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl, or isoindolyl.

The term"Q"refers to 5-or 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein nitrogen atom may be in turn substituted with Cl4 alkyl, phenyl, benzyl, or -C (=O) Cl4 alkyl. The example of Q is 2-, 3-, or 4-piperidinyl, 1-, or 2-pyrrolidinyl, morpholinyl, thiomorpholinyl, dioxolanyl, imidazolidinyl, oxathiolanyl, oxazolidinyl,

tetrahydrofuryl, or 2-oxo-1-pyrrolidinyl.

The term"halo"refers to fluoro, chloro, bromo, or iodo.

The term"pharmaceutically acceptable salts"refers to those salts which possess the biological effectiveness and properties of the parent compound and which are not biologically or otherwise undesirable.

Throughout this application, abbreviations which are well known to one of ordinary skill in the art may be used, such as"Ph"for phenyl,"Me"for methyl, etc.

Examples of preferred compounds of the present invention are: 1. N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4-thiadiazol-2-yl)-2-ethoxy-1- naphthamide, 2. N- (5- {[3-(cyclohexylamino) propyl] amino}-1, 3- dihydro-2-benzofuran-5-carboxamide, 3. N-{5-[(3, 3-diphenylpropyl) amino]-1, 3-dihydro-2- benzofuran-5-carboxamide, 4. N-15- [ (2,2-diphenylethyl) amino]-1,3,4-thiadiazol-2-yl}-1,3-dioxo-1,3-dihydro-2- benzofuran-5-carboxamide, [5- (undecylamino)-1,3, 4-thiadiazol-2-yl]-1,3-dihydro-2-benzofuran- 5-carboxamide, 6. N-[5-({[(2-R)-6, 6-dimethylbicyclo 4-thiadiazol- 2-yl]-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide, 3,4-thiadiazol-2-yl)-1,3-dihydro-2- benzofuran-5-carboxamide, 8. N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3- dihydro-2-benzofuran-5-carboxamide, 9. (E)-N-(5-{[3-(cyclohexylamino) propyl] amino}-1,3,4-thiadiazol-2-yl)-9- octadecenamide, 10.2-ethoxy-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol-2-yl)-1- naphthamide, 11.2,6-dichloro-N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4-thiadiazol-2- yl) benzamide, 12. N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-2-ethoxy-1-naphtha mide, 13. N-[5-({[(2R)-6, 6-dimethylbicyclo [3.1. 1]hept-2-yl]methyl}amino)-1, 3,4-thiadiazol- 2-yl]-2-ethoxy-1-naphthamide, 14. (E)-N-(5-{[4-(aminosulfonyl)benzyl]amino}-1, 3,4-thiadiazol-2-yl)-9- octadecenamide, 15. N- {5- [(2,2-diphenylethyl) amino]-1, 3,4-thiadiazol-2-yl}-2-ethoxy-1-naphthamide,

16. (E)-N-(5-{[3-(cyclohexylamino) propyl] amino}-1,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide, amino]-1,3,4-thiadiazol-2-yl} benzamide, amino]-1, 3,4-thiadiazol-2-yl} benzamide, 19. (E)-N- {5- [ (1,3-benzodioxol-5-ylmethyl) amino]-1, 3,4-thiadiazol-2-yl}-9- octadecenamide, 20. N- (5-{[4-(aminosulfonyl) benzyl] amino}-1, 3,4-thiadiazol-2-yl)-2,6- dichlorobenzamide, 21.2,6-dichloro-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol-2- yl) benzamide, amino]-1, 3,4-thiadiazol-2-yl} benzamide, 23. N-15- [ (1,3-benzodioxol-5-ylmethyl) amino]-1, 3, 4-thiadiazol-2-yl}-1, 3-dioxo-1,3- dihydro-2-benzofuran-5-carboxamide, 24.4-cyano-N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4-thiadiazol-2- yl) benzamide, 25. N-(50{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4-thiadiazol-2-yl)-5-nitro-2-furamide, 26.2, 6-dichloro-N-[5-({[(2R)-6, 6-dimethylbicyclo [3.1. 1]hept-2-yl]methyl} amino)- 1,3,4-thiadiazol-2-yl] benzamide, 27.4-cyano-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol-2-yl) benzamide, 28 N- [5- (cycloheptylamino)-1,3, 4-thiadiazol-2-yl]-1,3-dioxo-1, 3-dihydro-2- benzofuran-5-carboxamide, 29. N-15- [ (1,3-benzodioxol-5-ylmethyl) amino]-1, 3,4-thiadiazol-2-yl}-2,6- dichlorobenzamide, 30. N-{5-[(2,2-diphenylethyl)amino]-1,3,4-thiadiazol-2-yl}-2-met hoxybenzamide, 31. (E)-N-(5-{[4-(aminosulfonyl)benzyl]amino}-1, 3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide, 32. (E)-N-[5-({[(2R)-6, 6-dimethylbicyclo [3.1. 1]hept-2-yl]methyl}amino)-1, 3,4- thiadiazol-2-yl]-9-octadecenamide, 33. (E)-N-(5- {[2-(lH-indol-3-yl) ethyl] amino}-1,3,4-thiadiazol-2-yl)-9- octadecenamide, 34. (E)-N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-9-octadecenamide, 35. (E)-N- {5- [ (4-fluorobenzyl) amino]-1,3,4-thiadiazol-2-yl}-9-octadecenamide, 36. or 37. N- (5-1 [4- (aminosulfonyl) benzyll aminol-1,3,4-thiadiazol-2-yl)-2-ethoxy-1- naphthamide.

Examples of more preferred compounds of the present invention are:

1. N- (5- {[3-(cyclohexylamino) propyl] amino}-1, 3,4-thiadiazol-2-yl)-2-ethoxy-1- naphthamide, 2. N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3- dihydro-2-benzofuran-5-carboxamide, 3. N-{5-[(3,3-diphenylpropyl)amino]-1,3,4-thiadiazol-2-yl}-1,3- dioxo-1,3-dihydro-2- benzofuran-5-carboxamide, 4. N-{5-[(2,2-diphenylpropyl)amino]-1,3,4-thiadiazol-2-yl}-1,3- dioxo-1,3-dihydro-2- benzofuran-5-carboxamide, 3, 4-thiadiazol-2-yl]-1, 3-dihydro-2-benzofuran- 5-carboxamide, 6. N- [5- ( { [ (2R)-6,6-dimethylbicyclo 4-thiadiazol- 2-yl]-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide, 7. 1,3-dioxo-N-{5-[(4-phenylbutyl)amino]-1,3,4-thiadiazol-2-yl} -1,3-dihydro-2- benzofuran-5-carboxamide, 8. N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3- dihydro-2-benzofuran-5-carboxamide, or 9. (E)-N-(5-{[3-(cyclohexylamino) propyl] amino}-1,3,4-thiadiazol-2-yl)-9- octadecenamide.

The compounds of the present invention and pharmaceutically acceptable salts thereof are useful as antiviral agents. Thus, these compounds are useful to combat viral infections in animals, including man. Specifically, these compounds have anti-viral activity against the herpes virus, cytomegalovirus (CMV). Many of these compounds are also active against other herpes viruses, such as the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, and the human herpes virus type 8 (HHV-8).

Also, while many of the compounds of the present invention have shown activity against the CMV polymerase, these compounds may be active against the cytomegalovirus by this or other mechanisms of action. Thus, the description below of these compounds'activity against the CMV polymerase is not meant to limit the present invention to a specific mechanism of action.

The compounds of the present invention are tested in an polymerase assay to show activity described below, which is indicative of a compound's activity and thus of its use as an anti-viral agent.

The HCMV polymerase assay is performed using a scintillation proximity assay (SPA) as described in several references, such as N. D. Cook, et al., Pharmaceutical Manufacturing International, pages 49-53 (1992); K Takeuchi,

Laboratory Practice, September issue (1992); US Patent No. 4,568,649 (1986); which are incorporated by reference herein. Reactions are performed in 96-well plates.

The assay is conducted in 100 ul volume with 5.4 mM HEPES (pH 7.5), 11.7 mM KC1,4.5 mM MgCl2,0.36 mg/ml BSA, and 90 nM 3H-dTTP. Assays are run with and without CHAPS, (3- [ (3-Cholamidopropyl)-dimethylammonio]-1-propane- sulfonate) at a final concentration of 2 mM. HCMV is diluted in enzyme dilution buffer containing 50% glycerol, 250 mM NaCl, 10 mM HEPES (pH 7.5), 100 ug/ml BSA, and 0.01% sodium azide. The HCMV polymerase, which is expressed in recombinant baculovirus-infected SF-9 cells and purifie according to literature procedures, is added at 10% (or 10 ul) of the final reaction volume, i. e., 100 ul.

Compounds are diluted in 50% DMSO and 10 ul are added to each well. Control wells contain an equivalent concentration of DMSO. Unless noted otherwise, reactions are initiated via the addition of 6 nM biotinylated poly (dA)-oligo (dT) template/primer to reaction mixtures containing the enzyme, substrate, and compounds of interest. Plates are incubated in a 25°C or 37°C H20 bath and terminated via the addition of 40 ul/reaction of 0.5 M EDTA (pH 8) per well.

Reactions are terminated within the time-frame during which substrate incorporation is linear and varied depending upon the enzyme and conditions used, i. e., 30 min. for HCMV polymerase. Ten ul of streptavidin-SPA beads (20 mg/ml in PBS/10% glycerol) are added following termination of the reaction. Plates are incubated 10 min. at 37°C, then equilibrated to room temperature, and counted on a Packard Topcount. Results of the testing of compounds of the present invention in this assay are shown in TABLE 1 below.

These compounds of the present invention are administered in a pharmaceutical composition containing the compound in combination with a suitable excipient, the composition being useful in combating viral infections. Pharmaceutical compositions containing a compound appropriate for antiviral use are prepared by methods and contain excipients which are well known in the art. A generally recognized compendium of such methods and ingredients is Remington's Pharmaceutical Sciences by E. W. Martin (Mark Publ. Co., 15th Ed., 1975), which is hereby incorporated by reference herein.

The quantity of active component, that is the compounds of formula I according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application method, the potency of the particular compound and the desired concentration.

Generally, the quantity of active component will range between 0.5% to 90% by

weight of the composition.

The compounds of the present invention are administered parenterally (for example, by intravenous, intraperitoneal or intramuscular injection), topically, orally, or rectally, depending on whether the preparation is used to treat internal or external viral infections.

For internal infections, the compositions are administered orally or parenterally at dose levels, calculated as the free base, of about 0.1 to 300 mg/kg, preferably 1.0 to 30 mg/kg of mammal body weight, and are used in man in a unit dosage form, administered one to four times daily in the amount of 1 to 1000 mg per unit dose.

For parenteral administration or for administration as drops, as for eye infections, the compounds are presented in aqueous solution in a concentration of from about 0.1 to 10%, more preferably about 0.1 to 7%. The solution may contain other ingredients, such as emulsifiers, antioxidants or buffers.

The exact regimen for administration of the compounds and compositions disclosed herein will necessarily be dependent upon the needs of the individual subject being treated, the type of treatment and, of course, the judgment of the attending practitioner.

The following Scheme outlines the preparation of the compounds of the present invention.

SCHEME I In Scheme I, Y is-NHRl, or , Rl, Rx and X are as defined previously. The synthesis of structures 3 and 4, the compounds of the present invention, required two or three steps. 2-Amino-5-bromo-1,3,4-thiadiazole 2 is prepared through bromination of commercially available 2-amino-1,3,4-thiadiazole.

Compound 3 is prepared through direct bromide displacement of thiadiazole 2 with

an appropriate amine. Compound 3 then react with an appropriate acid chloride to provide compound 4.

It will be apparent to those skilled in the art that the described synthetic procedures are merely representative in nature and that alternative synthetic processes are known to one of ordinary skill in organic chemistry.

The compounds and their preparations of the present invention will be better understood in connection with the following examples, which are intended as an illustration of and not a limitation upon the scope of the invention.

EXAMPLE 1 Preparation of starting material 5-bromo-1,3,4-thiadiazol-2- ylamine.

To a stirred solution of 2-amino-1,3,4-thiadiazole (40.5 g) in 250 ml of acetic acid is added 22.7 ml of bromine over about 20 minutes. The flask is surrounded by an ice bath during the addition to maintain the reaction temperature near 25 °C.

Following the addition, the ice bath is removed and the clear red solution stirred at ambient temperature for 18 hours, then added to 1L of cracked ice. Excess bromine is quenched with NaHSOs, and 40 ml of 50% aqueous NaOH is added. The precipitated solid is isolated by filtration and washed well with water, then dissolved in 300 ml of water containing 40 ml concentrated. HC1. The solution is filtered from a small amount of solid, then 87 g of K2HPO4 in a small quantity of water is added.

The resulting slurry is chilled in ice and filtered, and the solid washed well with water. Recrystallization of the product from 400 ml of ethanol provides 26.3 g of the title compound.

1NMR (DMSO-d6) 8 7.51 ppm.

EXAMPLE 2 Preparation of tert-Butyl 4- (5-amino-1,3,4-thiadiazol-2-yl) tetrahydro- 1(2H)-pyrazinecarboxylate.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine (9.27 g), Boc-piperazine (11.51 g), and K2HPO4 (13.4 g) in 30 ml of DMF is heated at 100 °C under argon for four hours, then cooled and added to 100 g of ice. The mixture is extracted with ethyl acetate, and the organic phase washed twice with water and dried (MgSO4).

Following removal of the solvent under reduced pressure, the residue is flash chromatographed on silica using 4% methanol in dichloromethane to afford 8.32 g of the title compound as a solid. Recrystallization from 240 ml of 1: 1 acetonitrile- toluene provides 6.65 g of solid.

'NMR 8 1.47,3.34,3.53,4.8 ppm IR 3411,3132,1698,1676,1500,1427,1251,1167 ci~ EI HRMS m/z found: 285.1277 M. p. 215-216 °C.

EXAMPLE 3 Preparation of N- (5-Amino-1,3,4-thiadiazol-2-yl)-N-phenethylamine.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine (360 mg), phenethylamine (0.38 ml), and K2HPO4 (522 mg) in 2 ml of DMF is heated under nitrogen at 100 °C for two hours, then partitioned between water and ethyl acetate. The organic phase is washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. Flash chromatography of the residue on silica using 4-5% methanol in dichloromethane provides 261 mg of the title compound. Recrystallization of 238 mg of this from 10 ml of 1: 1 acetonitrile toluene affords 205 mg of crystals.

'H NMR 8 2.92,3.50,7.2-7.3 ppm IR 3186,1565,1505 cm~ EI MS m/z 221 M. p. 156-157 °C Anal. Found: C, 54.51; H, 5.47; N, 25.26; S, 14.30.

EXAMPLE 4 Preparation of 5-Morpholino-1,3,4-thiadiazol-2-ylamine.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine, K2HPO4 (5.7 g), and 5.3 ml of morpholine in 20 ml of DMF is heated at 80 °C under nitrogen for 18 hours, then diluted with 50 ml of water. The clear solution is placed in a continuous extractor

and extracted with a brisk flow of dichloromethane for 18 hours. The solution is dried over MgSO4 and concentrated under reduced pressure, with toluene azeotropes to remove DMF. Recrystallization of the residual solid from 50 ml of acetonitrile and 100 ml of toluene affords 3.92 g of the title compound.

'H NMR 8 3.34,3.80 ppm IR 1528,1499,1448,1245,1112,1036,906 cni 1 EI MS m/z 186 Anal. Found: C, 38.67; H, 5.48; N, 30.17; S, 17.18.

EXAMPLE 5 Preparation of tert-Butyl N- {2- [ (5-amino-1,3,4-thiadiazol-2- yl)amino] ethyl} carbamate.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine (5.40 g), K2HPO 4 (7.84 g), and Boc-ethylenediamine (9.6 g) in 20 ml of DMF is stirred at ambient temperature for 18 hours. The solid paste obtained is recrystallized from 100 ml of acetonitrile and 100 ml of water to provide 6.18 g (79%) of the title compound.

'H NMR (MeOH-d4) 8 1.40,3.2-3.3 ppm IR 2989,1676,1577,1512,1366 cm-' EI MS m/z 260 M. p. 219-220 °C.

EXAMPLE 6 Preparation of N- [5- (Cycloheptylamino)-1,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide.-ethoxy-1-naphthoyl).

cooled to 0 °C, is added a solution of 469 mg of 2-ethoxy-1-naphthoyl chloride in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure. Addition of water and ethyl acetate to the residue provides a solid, which is filtered, washed with ethyl acetate and water, and dried under vacuum to afford 200 mg of the title compound as a white solid.

'H NMR (CDC19) 8 1.50,1.4-1.8,2.1,3.6,4.26,7.3-7.6,7.8,8.0 ppm HRMS (m+H) 411.1875.

EXAMPLE 7 Preparation of N- [5- (Cycloheptylamino)-1,3,4-thiadiazol-2-yl]-2- methoxybenzamide.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine (720 mg), K2HPO4 (780 mg), and cycloheptylamine (0.51 mg) in 5 ml of DMF is stirred at 60 °C for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added 0.30 ml of o-anisoyl chloride. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The precipitated solid is filtered, washed with water, and dried under vacuum to afford 641 mg of the title compound.

'H NMR (CDCl3) 8 1.4-1.7,2.1,3.6,4.09,7.0-7.2,7.6,8.25 ppm HRMS m/z 346.1469.

EXAMPLE 8 Preparation of N- {5-[(2,2-Diphenylethyl) amino]-1,3,4-thiadiazol-2-yl}-2- ethoxy-1-naphthamide.

A mixture 5-bromo-1,3,4-thiadiazol-2-ylamine (720 mg), K2HPO4 (780 mg), and 2,2-diphenylethylamine (789 mg) in 5 ml of DMF is stirred at 60 °C for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this

solution, cooled to 0 °C, is added a solution of 2-ethoxy-l-naphthoyl chloride (469 mg) in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 947 mg of the title compound.

'H NMR (CDC13) 8 1.43,4.02,4.15,4.26,4.44,7.2-7.6,7.8-8.0 ppm HRMS (m+H) 495.1846.

EXAMPLE 9 Preparation of 2-Ethoxy-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4- thiadiazol-2-yl)-1-naphthamide.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine (720 mg), K2HPO4 (780 mg), and tryptamine (641 mg) in 5 ml of DMF is stirred at 60 °C for 12 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 469 mg of 2-ethoxy-1-naphthoyl chloride in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 866 mg of white solid. Column chromatography of 249 mg of this on silica, using 1.5-4% methanol in dichloromethane, provides 191 mg of the title compound.

'H NMR (CDC19) 8 1.43,3.16,3.70,4.26,7.0-7.2,7.3-7.4,7.5,7.6,7.8,8.0 ppm HRMS (m+H) 458.1655.

EXAMPLE 10 Preparation of N- [5- ( { [ (2R)-6,6-Dimethylbicyclo [3.1.1] hept-2- yl] methyl} amino)-1,3,4-thiadiazol-2-yl]-2-ethoxy-1-naphthamide.

A mixture of 5-bromo-1,3,4-thiadiazol-2-ylamine (720 mg), K2HPO4 (780 mg),

and myrtanylamine (0.67 mg) in 5 ml of DMF is stirred at 60 °C for 12 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 2-ethoxy-1-naphthoyl chloride (469 mg) in 5 ml of chloroform.

The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 846 mg of solid. Column chromatography of 249 mg of this on silica, using 2-4% methanol in dichloromethane, provides 220 mg of the title compound.

'H NMR (CDCl3) 8 1.07,1.23,1.44,1.8-2.1,2.4,3.3,4.27,7.2-7.6,7.8,8.0 ppm HRMS (m+H) 451.2163.

EXAMPLE 11 The Following 1,3,4-Thiadiazoles of the Present Invention Are Prepared by General Procedure Described Below.

To each 48 solutions of 5-bromo-1,3,4-thiadiazol-2-ylamine (234 mg, 1.3 mmol) in 1.5 ml of DMF is added K2HPO4 (272 mg) and 1.3 mmol of the following amines respectively: phenethylamine, 2-furylmethylamine, 1- (3-aminopropyl)-2-pyrrolidinone, 2-pyridinylmethylamine, N-(2-aminoethyl)-N-phenylamine, 2-(lH-indol-3-yl) ethylamine, cycloheptylamine, cyclohexylmethylamine, (lS, 2R, 5S)-6,6-dimethylbicyclo [3.1.1] hept-2- yl] methylamine, 2- (1-pyrrolidinyl) ethylamine, tetrahydro-2-furanylmethylamine, 4-pyridinylmethylamine, 1,3-benzodioxol-5-ylmethylamine, 2-morpholinoethylamine, 1-naphthylmethylamine, 4-fluorobenzylamine, 3-pyridinylmethylamine, 2-piperidinoethylamine, 2-ethylhexylamine, 4- (2-aminoethyl) benzenesulfonamide, N- (3-aminopropyl)-N-cyclohexylamine, 3,4-dichlorobenzylamine, 3,4-dimethoxybenzylamine, 4-phenylbutylamine, 2,2-diphenylethylamine, undecylamine, 3,3-diphenylpropylamine, 2- (2-thienyl) ethylamine, 4- (aminomethyl) benzenesulfonamide, 3- (4-methylpiperazino) propylamine, 3-aminopropanenitrile, 2- (phenylsulfanyl) ethylamine, 2-thienylmethylamine, N- (2-aminoethyl) acetamide, 3- (lH-imidazol-1-yl) propylamine, tert-butyl 3-aminopropanoate, cyclopropylamine, cyclopropylmethylamine, 2- (lH-imidazol-4-yl) ethylamine, 2- (ethylsulfanyl) ethylamine, cyclobutylamine, 2-(1-methyl-2-pyrrolidinyl) ethylamine,(1-methyl-2-pyrrolidinyl) ethylamine, 2,3-dihydro-lH-inden-1-ylamine, neopentylamine, 1,2,3,4-tetrahydro-l-naphthalenamine, ethyl 4-aminotetrahydro-l (2H)- pyridinecarboxylate, 1-benzyl-4-piperidinylamine, and N- (2-aminoethyl)-N, N- dimethylamine.

The resultant 48 mixtures are heated at 60 °C for 3 hours to provide a DMF

solutions of the corresponding substituted aminothiadiazole intermediates. The solutions of intermediate aminothiadiazoles are diluted with pyridine to a volume of 10.0 ml, and solids are removed by centrifugation. The supernatants are aliquoted into wells of 96-well plates (0.40 ml per well) respectively, and to each well is added 0.26 ml of a 0.2 M chloroform solution of the following acid chlorides respectively : 2, 4-difluorobenzoyl chloride, 2-methoxybenzoyl chloride, 4-bromobenzoyl chloride, 4-methylbenzoyl chloride, 5-chloropentanoyl chloride, 4-cyanobenzoyl chloride, 3-nitrobenzoyl chloride, 3,5-difluorobenzoyl chloride, (E)-3- (2-chlorophenyl)-2-propenoyl chloride, 2-ethoxy-1-naphthoyl chloride, (Z)-9-octadecenoyl chloride, 2,6-dichlorobenzoyl chloride, 3,4-dichlorobenzoyl chloride, 4- (trifluoromethyl) benzoyl chloride, (E)-3-phenyl-2-propenoyl chloride, 4-iodobenzoyl chloride, 1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carbonyl chloride, 4- (fluorosulfonyl) benzoyl chloride, 2,4,6-triisopropylbenzoyl chloride, 5-nitro-2-furoyl chloride, and 1-benzothiophene-2-carbonyl chloride.

The plates are shaken at intervals to effect mixing of reactants, and the acylation is allowed to proceed at room temperature overnight. Removal of the solvents in a stream of air or under vacuum then affords the compounds listed in TABLE 1.

AH the amines and acid chlorides used above are either commercially available or can be easily prepared by one having ordinary skill in the organic chemistry art utilizing well known procedures.

In TABLE 1,"MS"refers to mass spectral data,"% inhib"refers to percentage of inhibition at 25 uM concentration in CMV polymerase assay.

TABLE 1 MS % Inhib 1 (E)-N- (5- { [3- (cyclohexylamino) propyl] amino}-1,3,4- thiadiazol-2-yl)-9-octadecenamide 520 100.2 2 N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4-thiadiazol- 2-yl)-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide---100 .1 3 N- (5- [ (cyclohexyhnethyl) aminol-1,3,4-thiadiazol-2-yl}-1,3- dioxo-1,3-dihydro-2-benzofuran-5-carboxamide 419 100.0 4 1,3-dioxo-N- [5- (undecylamino)-1,3,4-thiadiazol-2-yl]-1,3- dihydro-2-benzofuran-5-carboxamide 443 100.0 5 (E)-Nq5-{[2-(1-methyl-2-pyrrolidinyl) ethyl] amino}-1,3,4- thiadiazol-2-yl)-9-octadecenamide 492 99.9 6 N- {5-[(2-anilinoethyl) amino]-1, 3,4-thiadiazol-2-yl}-1,3-

dioxo-1, 3-dihydro-2-benzofuran-5-carboxamide, 410 99.9 7 N- {5- [ (4-iluorobenzyl) amino]- l, 3, 4-thiadiazol-2-yl}-1, 3- dioxo-1, 3-dihydro-2-benzofuran-5-carboxamide 399 99.8 8 N- (5- [ (l-naphthylmethyl) amino]-1,3,4-thiadiazol-2-yl}- 1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide 431 99.8 9 1,3-dioxo-N- (5-{[2-(2-thienyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl)-1,3-dihydro-2-benzofuran-5- carboxamide 401 99.8 10 N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol-2- yl)-1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 434 99.7 11 1, 3-dioxo-N-{5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2- yl}-1,3-dihydro-2-benzofuran-5-carboxamide 421 99.6 12 N-{5-[(3,4-dichlorobenzyl)amino]-1, 3,4-thiadiazol-2-yl}- 1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 449 99.5 13 N-{5-[(3,3-dichlorobenzyl)amino]-1,3,4-thiadiazol-2- yl}-1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 483 99.3 14 (E)-N-(5-{[3-(4-methylpiperazino)propyl]amino}-1, 3,4- thiadiazol-2-yl)-9-octadecenamide 521 99.0 15 N- (5-{[4-(aminosulfonyl) phenethyl] amino}-1, 3,4-thiadiazol- 2-yl)-1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 474 98.8 16 N-{5-[(3,4-dichlorobenzyl)amino]-1, 3,4-thiadiazol-2-yl}- 1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide 441 98.7 17 N- {5- [ (2,2-diphenylethyl) amino]-1, 3,4-thiadiazol-2-yl}- 1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 471 98.6 18 (E)-N-(5-{[4-(aminosulfonyl)benzyl[amino}-1, 3,4- thiadiazol-2-yl)-9-octadecenamide---98.3 19 (E)-N-(5-{[2-(1-pyrrolidinyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-9-octadecenamide 478 97.7 20 N-{5-[(1,3-benzodioxol-5-ylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-1,3-dioxo-1,3-dihydro-2- benzofuran-5-carboxamide 425 97.7 21 1,3-dioxo-N-[5-(1,2,3,4-tetrahydro-1-naphthalenylamino)- 1,3,4-thiadiazol-2-yl]-1,3-dihydro-2-benzofuran-5- carboxamide 421 97.4 22 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}- amino)-1,3,4-thiadiazol-2-yl]-2-methoxybenzamide 387 97.2

23 (E)-N-(5-{[2-(dimethylamino) ethyl] amino}-1,3,4-thiadiazol- 2-yl)-9-octadecenamide 452 97.0 24 1,3-dioxo-N- [5- (phenethylamino)-1,3,4-thiadiazol-2-yl]- 1,3-dihydro-2-benzofuran-5-carboxamide 395 95.6 25 N-[5-({[(2R)-6, 6-dimethylbicyclo [3.1. l] hept-2-yl] methyl}- amino)-1,3, 4-thiadiazol-2-yl]-1,3-dioxo-1, 3-dihydro-2- benzofuran-5-carboxamide 425 93.9 26 N- (5-{[4-(aminosulfonyl) benzyl] nmino}-1, 3,4-thiadiazol- 2-yl)-2-ethoxy-1-naphthamide 484 93.1 27 N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4- thiadiazol-2-yl)-2-ethoxy-1-naphthamide 454 92.9 28 (E)-N- [5- (cyclopropylamino)-1,3,4-thiadiazol-2-yl]- 9-octadecenamide 421 92.6 29 N- [5- (cycloheptylamino)-1,3, 4-thiadiazol-2-yl]-1, 3-dioxo- 1,3-dihydro-2-benzofuran-5-carboxamide 387 92.4 30 N- (5-1 [4- (aminosulfonyl) benzyllaniinol-1,3,4-thiadiazol- 2-yl)-2,6-dichlorobenzamide 458 91.8 31 (E)-N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-9- octadecenamide 477 91.8 32 (E)-N-(5-{[4-(aminosulfonyl) benzyl] amino}-1, 3,4- thiadiazol-2-yl)-3-phenyl-2-propenamide 416 90.6 33 1, 3-dioxo-N-(5-{[2-(phenylsulfanyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-1,3-dihydro-2-benzofuran-5-carboxamide 425 90.1 34 (E)-3-(2-chlorophenyl)-N-{5-[(cyclopropylmethyl) amino]- 1,3,4-thiadiazol-2-yl}-2-propenamide 335 89.9 35 N-(5-{[4-(aminosulfonyl)benzyl]amino}-1, 3,4-thiadiazol-2- yl)-2,4,6-triisopropylbenzamide 516 89.7 36 N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4-thiadiazol- 2-yl)-2,4,6-triisopropylbenzamide 486 87.6 37 2,6-dichloro-N-(5-{[3-(cyclohexylamino) propyl] amino}- 1,3,4-thiadiazol-2-yl) benzamide 428 87.4 38 (E)-N-15- [ (2,2-diphenylethyl) amino]-1,3,4-thiadiazol-2-yl}- 9-octadecenamide 561 87.3 39 1, 3-dioxo-N-{5-[(2-thienylmethyl)amino]-1, 3,4-thiadiazol- 2-yl}-1,3-dihydro-2-benzofuran-5-carboxamide 387 87.1 40 N- [5- (2, 3-dihydro-IH-inden-1-ylamino)-1,3,4-thiadiazol-2-

yl]-1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 407 86.3 41 (E)-N-(5-{[2-(2-thienyl) ethyl] amino}-1,3,4-thiadiazol-2- yl)-9-octadecenamide 491 85.7 42 (E)-N-{5-[(2-thienylmethyl) amino]-1,3,4-thiadiazol-2-yl}- 9-octadecenamide 477 84.6 43 N-{5-[(1,3-benzodioxol-5-ylmethyl)amino]-1, 3,4-thiadiazol- 2-yl}-2-ethoxy-1-naphthamide 449 83.9 44 N-{5-[(1-naphthylmethyl)amino-1,3,4-thiadiazol-2-yl}- 5-nitro-2-furamide 396 83.3 45 N-{5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4-thiadiazol-2-yl}- 2-ethyoxy-1-naphthamide 488 83.1 46 4-cyano-N- (5- [ (3,3-diphenylpropyl) amino]-1, 3,4-thiadiazol- 2-yl} benzamide 440 82.3 47 N-(5-{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4-thiadiazol-2- yl)-5-nitro-2-furamide 399 81.6 48 (E)-N- {5- [ (4-fluorobenzyl) amino]-1,3,4-thiadiazol-2-yl}- 9-octadecenamide 489 81.5 49 4- ({[5-(undecylAmino)-1, 3,4-thiadiazol-2-yl] amino}- carbonyl) benzenesulfonyl fluoride---80.3 50 (E)-N-(5-{[4-(aminosulfonyl) phenethyl] amino}-1,3,4- thiadiazol-2-yl)-3-phenyl-2-propenamide 430 79.8 51 (E)-N- [5- (undecylamino)-1,3,4-thiadiazol-2-yl]-9- octadecenamide 535 79.5 52 N- {5- [ (4-phenylbutyl) amino]-1,3,4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide---78.7 53 (E)-N-{5-[(1, 3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-9-octadecenamide 515 77.9 54 1,3-dioxo-N- {5- [ (4-pyridinylmethyl) amino]-1,3,4- thiadiazol-2-yl}-1, 3-dihydro-2-benzofuran-5-carboxamide 382 77.7 55 N-{5-[(2,2-diphenylthyl)amino]-1,3,4-thiadiazol-2-yl}- 2-ethoxy-1-naphthamide 495 77.6 56 2, 6-dichloro-N-{5-[(2, 2-diphenylethyl) amino]-1,3,4- thiadiazol-2-yl} benzamide 469 77.4 57 N-(5-{[4-(aminosulfonyl)benzyl]amino}-1, 3,4- thiadiazol-2-yl)-4-iodobenzamide 516 76.3 58 (E)-N-(5-{[2-(phenylsulfanyl)ethyl]amino}-1, 3,4-

thiadiazol-2-yl)-9-octadecenamide 517 75.8 59 4-iodo-N- {5- [ (4-phenylbutyl) amino]-1,3,4-thiadiazol- 2-yl} benzamide 479 74.6 60 5-nitro-N- [5- (undecylamino)-1,3,4-thiadiazol-2-yl]- 2-furamide-74.5 61 N- {5- [ (3,3-diphenylpropyl) amino]-1,3,4-thiadiazol- 2-yl}-2-ethoxy-1-naphthamide 509 74.2 62 N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4- thiadiazol-2-yl)-1-benzothiophene-2-carboxamide 416 74.0 63 amino]- 1,3,4-thiadiazol-2-yl} benzamide 483 73.8 64 (E)-N-{5-[(3,3-diphenylpropyl)amino]-1,3,4- thiadiazol-2-yl}-9-octadecenamide 575 73.6 65 4-cyano-N- [5- (undecylamino)-1,3,4-thiadiazol- 2-yl] benzamide 400 72.2 66 2-ethoxy-N- {5- [ (3-pyridinylmethyl) amino]-1,3,4- thiadiazol-2-yl}-1-naphthamide 406 71.9 67 (E)-3-(2-chlorophenyl)-N-{5-[(4-fluorobenzyl)amino]- 1,3,4-thiadiazol-2-yl}-2-propenamide 389 71.7 68 N-(5-{[4-(aminosulfonyl)phenthyl]amino}-1, 3,4- thiadiazol-2-yl)-4-iodobenzamide 530 71.1 69 N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2-yl}- 2-ethoxy-1-naphthamide 434 70.6 70 2-ethoxy-N- {5-[(2-pyridinylmethyl) amino]-1, 3,4- thiadiazol-2-yll-l-naphthamide 406 70.4 71 2-ethyl-N-{5-[(4-fluorobenzyl)amino]-1, 3,4- thiadiazol-2-yl}-1-naphthamide 423 69.8 72 (E)-N-{5-[(3-pyridinylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-9-octadecenamide 470 69.3 73 amino]- 1,3,4-thiadiazol-2-yl} benzamide 449 69.1 74 4-cyano-N-{5-[(4-fluorobenzyl)amino-1, 3,4- thiadiazol-2-yl} benzamide 354 69.0 75 (E)-3-(2-chlorophenyl)-N-(5-{[3-(cyclohexylamino)- propyl] amino}-1,3,4-thiadiazol-2-yl)-2-propenamide 420 68.8 76 3,4-tetrahydro-1-naphthalenyl-

amino)-1,3,4-thiadiazol-2-yl] benzamide 419 68.5 77 (E)-3-phenylN-(5-{[2-(2-thienyl) ethyl] amino}-1,3,4- thiadiazol-2-yl)-2-propenamide 357 68.3 78 2-ethoxy-N- {5-[(2-thienylmethyl) amino]-1, 3,4-thiadiazol- 2-yl}-1-naphthamide 411 68.2 79 tert-butyl 3- ( {5- [ (E)-9-octadecenoylamino]-1,3,4- thiadiazol-2-yl} amino) propanoate---68.0 80 3-nitro-N- [5- (undecylamino)-1,3,4-thiadiazol-2-yl]- benzamide---67.9 81 (E)-3-phenyl-N- {5- [ (4-phenylbutyl) amino]-1,3,4- thiadiazol-2-yl}-2-propenamide 379 67.9 82 4-cyano-N-(5-{[2-(lH-indol-3-yl) ethyl] amino}- 1,3,4-thiadiazol-2-yl) benzamide 389 67.7 83 4-cyano-N- {5- [ (2,2-diphenylethyl) nmino]-1,3,4- thiadiazol-2-yl} benzamide 426 67.7 84 2,6-dichloro-N- {5- [ (4-pyridinylmethyl) amino]- 1,3,4-thiadiazol-2-yl} benzamide 380 67.6 85 N- {5- [ (1-benzyl-4-piperidinyl) amino]-1,3,4- thiadiazol-2yl}-1,3-dioxo-1,3-dihydro-2-benzofuran- 5-carboxamide 464 67.3 86 4-[(5-{[(2-ethoxy-1-naphthyl)carbonyl]amino}- 1,3, 4-thiadiazol-2-yl)amino]tetrahydro-1, (2H)- pyridinecarboxylate 470 67.0 87 N- (5-{[3-(lH-imidazol-1-yl) propyl] amino}-1, 3,4- thiadiazol-2-yl)-2,4,6-triisopropylbenzamide 455 67.0 88 (E)-N-(5-{[4-(aminosulfonyl)benzyl]amino}-1, 3,4- thiadiazol-2-yl)-3- (2-chlorophenyl)-2-propenamide 450 66.5 89 2-ethoxy-N-(5-{[2-(lH-imidazol-4-yl) ethyl] amino}- 1,3,4-thiadiazol-2-yl)-1-naphthamide 409 66.3 90 4-{[(5-{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) amino]carbonyl}benzenesulfonyl fluoride 446 66.1 91 ethyl 4-({5-[(E)-9-octadecenoylamino]-1, 3,4-thiadiazol- 2-yl}amino)tetrahydro-1(2H)-pyridinecarboxylate 272 66.1 92 4- thiadiazol-2-yl) benzamide 399 66.1 93 2-ethoxy-N-[5-(1, 2,3,4-tetrahydro- 1-naphthalenylamino)-

1,3,4-thiadiazol-2-yl]-1-naphthamide 445 66.0 94 (E)-3-phenyl-N- {5- [ (4-pyridinylmethyl) amino]-1,3,4- thiadiazol-2-yl}-2-propenamide 338 65.9 95 N- [5- (2, 3-dihydro-lH-inden-1-ylamino)-1,3,4-thiadiazol- 2-yl]-2-ethoxy-1-naphthamide 431 65.9 96 N-{5-[(1, 3-benzodioxol-5-ylethyl) amino]-1,3,4-thiadiazol- 2-yl}-2,6-dichlorobenzamide 423 65.9 97 2-ethyoxy-N-(5-{[2-(2-thienyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-1-naphthamide 425 65.8 98 (E)-3-(2-chlorophenyl)-N-(5-{[2-(lH-imidazol-4-yl) ethyl]- amino}-1, 3,4-thiadiazol-2-yl)-2-propenamide 375 65.7 99 2,6-dichloro-N-(5-{[3-(1H-imidazol-1-yl)propyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 397 65.6 100 (E)-N-{5-[(3,4-dimethoxybenzyl)amino]-1, 3,4-thiadiazol- 2-yl}-9-octadecenamide---65.1 101 2, 6-dichloro-N-{5-[(1-naphthylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 429 65.0 102 4-cyano-N-(5-{[2-(2-thienyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide 356 64.9 103 4-cyano-N- [5- (cycloheptylamino)-1,3,4-thiadiazol- 2-yl] benzamide 342 64.9 104 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-5- nitro-2-furamide 352 64.7 105 (E)-N- [5- (phenethylamino)-1,3,4-thiadiazol-2-yl]- 9-octadecenamide, 485 64.6 106 5-chloro-N- [5- (undecylamino)-1,3,4-thiadiazol-2- yl] pentanamide, 389 64.2 107 (E)-N- [5- (1,2,3,4-tetrahydro-1-naphthalenylamino)- 1,3,4-thiadiazol-2-yl]-9-octadecenamide 511 63.8 108 (E)-N- {5- [ (4-phenylbutyl) amino]-1,3, 4-thiadiazol-2-yl}- 9-octadecenamide 513 63.5 109 2,4, 6-triisopropyl-N-(5-{[2-(1-methyl-2-pyrrolidinyl)ethyl] amino}-1,3,4-thiadiazol-2-yl) benzamide 458 63.4 110 (E)-N-{5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4-thiadiazol- 2-yl}-3-(2-chlorophenyl)-2-propenamide 454 62.9 111 4-[({5-[(2, 2-diphenylethyl) amino]-1,3,4-thiadiazol-2-

yl} amino) carbonyl] benzenesulfonyl fluoride 483 62.6 112 N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4- thiadiazol-2-yl)-4- (trifluoromethyl) benzamide 428 62.5 113 (E)-N-{5-[(cyclopropylmethyl)amino]-1, 3,4-thiadiazol- 2-yl}-9-octadecenamide 435 62.2 114 (E)-3-phenyl-N-(5-{[2-(phenylsulfanyl) ethyl] amino}- 1,3,4-thiadiazol-2-yl)-2-propenamide 383 62.1 115 2,6-dichloro-N- [5- (2, 3-dihydro-lH-inden-1-ylamino)- 1,3,4-thiadiazol-2-yl] benzamide 405 62.0 116 N- {5-[(2-ethylhexyl) amino]-1, 3,4-thiadiazol-2-yl}- 1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide 401 61.9 117 (E)-N- {5- [ (1, 3-benzodioxol-5-ylmethyl) amino]- 1,3,4-thiadiazol-2-yl}-3- (2-chlorophenyl)-2-propenamide 415 61.5 118 2,6-dichloro-N- {5-[(2-thienylmetyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide 385 61.2 119 (E)-N-{5-[(1-naphthylmethyl)amino]-1, 3,4-thiadiazol- 2-yl}-9-octadecenamide 521 60.6 120 tert-butyl-3-[(5-{[(E)-3-phyenyl-2-propenoyl]amino}- 1,3,4-thiadiazol-2-yl) amino] propanoate 375 60.0 121 4-thiadiazol-2- yllbenzamide 411 60.0 122 N- {5- [ (3,4-dimethoxybenzyl) amino]-1, 3,4-thiadiazol- 2-yl}-2-ethoxy-1-naphthamide 465 59.5 123 (E)-N-(5-{[2-(acetylamino)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-9-octadecenamide 466 59.2 124 (E)-N-(5-{[3-(cyclohexylamino)propyl]amino}- 1,3,4-thiadiazol-2-yl)-3-phenyl-2-propenamide 386 59.2 125 (E)-N-(5-{[4-(aminosulfonyl)phenethyl]amino}-1, 3,4- thiadiazol-2-yl)-3- (2-chlorophenyl)-2-propenamide 464 58.9 126 N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4- thiadiazol-2-yl)-5-nitro-2-furamide 395 58.9 127 4-cyano-N-(5-{[3-(cyclohexylxmino) propyl] amino}- 1,3,4-thiadiazol-2-yl) benzamide 385 58.5 128 N-(5-{[4-(aminosulfonyl)phenethyl]amino}-1, 3,4- thiadiazol-2-yl)-2,4,6-triisopropylbenzamide 530 58.3 129 (E)-N-(5-{[2-(ethylsulfanyl)ethyl]amino}-1, 3,4-

thiadiazol-2-yl)-9-octadecenamide 469 58.3 130 (E)-N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}- 1,3,4-thiadiazol-2-yl)-3-phenyl-2-propenamide 372 58.2 131 5-nitro-N{5-[(4-phenylbutyl)amino]-1, 3,4- thiadiazol-2-yl}-2-furamide 388 58.0 132 ethyl 4- ( {5- [ (2,6-dichlorobenzoyl) amino]-1,3,4- thiadiazol-2-yl} amino) tetrahydro-l (2H)- pyridinecarboxylate 444 57.0 133 (E)-N-(5-{[3-(1H-imidazol-1yl)propyl]amino}- 1,3,4-thiadiazol-2-yl)-3-phenyl-2-propenamide 355 57.0 134 N- {5- [ (3, 4-dimethoxybenzyl) amino]-1,3,4- thiadiazol-2-yl}-4-iodobenzamide 497 56.9 135 3-nitro-N-(5-{[3-(2-oxo-1pyrrolidinyl)propyl]- amino}-1,3,4-thiadiazol-2-yl) benzamide 391 56.6 136 2-ethoxy-N- {5- [ (1-naphthylmethyl) amino]-1,3,4- thiadiazol-2-yl}-1-naphthamide 455 56.5 137 N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4- thiadiazol-2-yl)-3-nitrobenzamide 405 56.4 138 N-{5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2-yl}- 4-(trifluoromethyl) benzamide 421 56.2 139 (E)-3-phenyl-N-{5-[(2-pyridinylmethyl)amino]- 1,3,4-thiadiazol-2-yl}-2-propenamide 338 56.2 140 4-cyano-N- {5- [ (3,4-dichlorobenzyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide 404 56.2 141 2-ethyoxy-N-(5-{[2-(1H-indol-3-yl)ethyl]amino}- 1,3,4-thiadiazol-2-yl)-1-naphthamide 458 55.7 142 N- (5-{[4-(aminosulfonyl) phenethyl] nmino}-1, 3,4- thiadiazol-2-yl)-3,4-dichlorobenzamide 472 55.4 143 4-cyano-N- {5- [ (4-phenylbutyl) amino]-1,3,4- thiadiazol-2-yl} benzamide 378 55.4 144 4- thiadiazol-2-yl} benzamide 397 55.2 145 2-ethoxy-N- [5- (undecylamino)-1,3,4-thiadiazol- 2-yl]-1-naphthamide 469 54.9 146 2,6-dichloro-N- {5-[(2-cyanoethyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide 342 54.8

147 4-iodo-N- [5- (undecylamino)-1,3,4-thiadiazol-2- yl] benzamide 501 54.7 148 N-(5-{[2-(ethylsulfanyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-4-iodobenzamide 435 54.6 149 (E)-N-(5-{[2-(1H-indol-3-yl)ethyl]amino}-1,3,4- thiadiazol-2-yl)-9-octadecenamide 524 54.5 150 N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}- 1,3,4-thiadiazol-2-yl)-1-benzothiophene-2-carboxamide 402 54.5 151 N- {5- [ (l-benzyl-4-piperidinyl) amino]-1,3,4-thiadiazol- 2-yl}-2,6-dichlorobenzamide 462 54.0 152 N-(5-[[4-(aminosulfonyl)phenetyl]amino}-1, 3,4- thiadiazol-2-yl)-4-bromobenzamide 484 53.9 153 (E)-N-(5-{[2-(lH-indol-3-yl) ethyl] amino}-1,3,4- thiadiazol-2-yl)-3-phenyl-2-propenamide 390 53.7 154 (E)-3-(2-chlorophenyl)-N-{5-[(2,2-diphenylethyl) amino]- 1,3,4-thiadiazol-2-yl}-2-propenamide---53.6 155 4-cyano-N-{5-[(1-naphthylmethyl)amino]-1, 3,4-thiadiazol-2- yl} benzamide 386 53.3 156 4- thiadiazol-2-yl} benzamide 380 53.2 157 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-2-ethoxy-1- naphthamide 411 53.0 158 4-cyano-N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 371 52.9 159 4-bromo-N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 440 52.8 160 N- (5-1 [3- (cyclohexylamino) propyllamino)-1,3,4- thiadiazol-2-yl)-2,4-difluorobenzamide 396 52.6 161 (E)-3-(2-chlorophenyl)-N-{5-[(2-pyridinylmethyl) amino]- 1,3,4-thiadiazol-2-yl}-2-propenamide 372 51.9 162 N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4-thiadiazol-2- yl)-4-methylbenzamide 374 51.8 163 4-bromo-N- (5-{[2-(phenylsulfanyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 437 51.5 164 (E)-3- (2-chlorophenyl)-N- {5- [ (2-thienylmethyl) amino]-1,3,4- thiadiazol-2-yl}-2-propenamide 377 51.4

165 N-15- [ (1,3-benzodioxol-5-ylmethyl) amino]-1, 3,4-thiadiazol-2- yl}-5-chloropentanamide 369 51.3 166 (E)-N-[5-({[(2R)-6,6-dimethylbicyclo [3.1. l] hept-2-yl] methyl}- amino)-1,3,4-thiadiazol-2-yl]-9-octadecenamide 517 51.1 167 4-methyl-N- [5- (undecylamino)-1,3,4-thiadiazol-2- yl] benzamide 389 50.8 168 4-thiadiazol-2- yl} benzamide 421 50.8 169 2,4, 6-triisopropyl-N-(5-{[2-(1-pyrrolidinyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide 444 50.7 170 4-bromo-N-{5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2- yl} benzamide 433 50.5 171 (E)-N-{5-[(2-pyridinylmethyl) amino]-1,3,4-thiadiazol-2-yl}-9- octadecenamide 472 49.9 172 3,4-dichloro-N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 428 49.7 173 2,4, 6-triisopropyl-N-{5-[(1-naphthylmethyl)amino]01, 3,4- thiadiazol-2-yl} benzamide 487 49.5 174 2, 6-dichloro-N-{5-[(2-furylmethyl)amino]-1, 3,4-thiadiazol-2- yl} benzamide 369 49.5 175 4-thiadiazol-2- yl] benzamide 411 49.4 176 N-{5-[(2, 2-diphenylethyl) amino]-1,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide 527 49.4 177 N- {5-[(cyclopropylmethyl) amino]-1, 3,4-thiadiazol-2- yl}-2-ethoxy-1-naphthamide 369 49.0 178 (E)-N- {5- [ (1,3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-3-phenyl-2-propenamide 381 49.0 179 (E)-N-{5-[(2-anilinotethyl)amino]-1, 3,4-thiadiazol-2- yl}-9-octadecenamide 500 48.5 180 N- {5- [ (1, 3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-1-benzothiophene-2-carboxamide--8.4 181 N- 5- [ (1, 3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-4-methylbenzamide 369 48.3 182 N-15- [ (2,2-diphenylethyl) amino]-1,3,4-thiadiazol-2- yl}-2, 4-difluorobenzamide 437 48.2

183 5-chloro-N- {5- [ (3,3-diphenylpropyl) amino]-1, 3,4- thiadiazol-2-yl} pentanamide 429 48.1 184 1,3-dioxo-N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}- 1,3,4-thiadiazol-2-yl)-1, 3-dihydro-2-benzofuran-5-carboxamide 434 47.8 185 (E)-3-(2-chlorophenyl)-N-)50{[2-2-(2-thienyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-2-propenamide 391 47.6 186 5-chloro-N-{5-[(2,2-diphenylethyl)amino]-1,3,4-thiadiazol-2- yl} pentanamide 415 47.4 187 N-15- [ (2,2-diphenylethyl) amino]-1, 3,4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide-47.2 188 N-f5- [ (2,2-diphenylethyl) amino]-1,3,4-thiadiazol-2- yl}-3,5-difluorobenzamide 437 47.2 189 4-{[(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4- thiadiazol-2-yl) amino] carbonyl} benzenesulfonyl fluoride 442 47.1 190 N-{5-[(1-naphthylmethyl)amino]-1, 3,4-thiadiazol-2- yl}-3-nitrobenzamide 406 47.1 191 3,4-dichloro-N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]- amino}-1,3,4-thiadiazol-2-yl) benzamide 414 47.1 192 5-nitro-N- [5- (1,2,3,4-tetrahydro-l-naphthalenylamino)- 1,3,4-thiadiazol-2-yl]-2-furamide 386 47.0 193 (E)-3-(2-chlorophenyl)-N-(5-{[2-(ethylsulfanyl) ethyl]- amino}-1, 3,4-thiadiazol-2-yl)-2-propenamide 369 46.9 194 4-bromo-N- [5- (undecylamino)-1,3,4-thiadiazol-2- yl] benzamide 455 46.8 195 4-[({5-[(1-naphthylmethyl)amino]-1, 3,4-thiadiazol-2- yl} amino) carbonyl] benzenesulfonyl fluoride 443 46.7 196 (E)-3- (2-chlorophenyl)-N- [5- (cycloheptylamino)-1,3,4- thiadiazol-2-yl]-2-propenamide 377 46.2 197 2, 4-difluoro-N0{5-[(4-phenylbutyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 389 46.2 198 4-iodo-N-(5-{[2-(phenylsulfanyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide---46.0 199 (E)-N- [5- (cyclobutylamino)-1,3,4-thiadiazol-2-yl]-9- octadecenamide 435 46.0 200 5-chloro-N-{5-[(1-naphthylmethyl) amino]-1, 3, 4- thiadiazol-2-yl} pentanamide 375 45.3

201 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2- yll-3-nitrobenzamide 362 45.3 202 3,4-dichloro-N-(5-{[3-(1H-imidazol-1-yl)propyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 397 45.0 2-\03 4-iodo-N-(5-{[3-(2-oxo-1-pyrrolidionyl)propyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 472 45.0 204 4- [({5-[(2-anilinoethyl) amino]-1, 3,4-thiadiazol-2- yl}amino)carbonyl]benzenesulfonyl fluoride 422 45.0 205 2,4-difluoro-N-(5-{[2-(phenylsulfanyl) ethyl] amino}- 1,3,4-thiadiazol-2-yl) benzamide 393 44.9 206 2-ethoxy-N-(5-{[2-(phenylsulfanyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-1-naphthamide 451 44.9 207 N- {5- [ (3,4-dichlorobenzyl) amino]-1, 3,4-thiadiazol-2-yl}-2- ethoxy-1-naphthamide 473 44.7 208 3-(2-chlorophenyl)-N-(5-{[3-(2-oxo-1-pyrrolidinyl)- propyl] amino}-1,3,4-thiadiazol-2-yl)-2-propenamide 406 44.7 209 N-[5-({[(2R)-6,6dimethylbicyclo [3.1. llhept-2-yllmethyll- amino)-1, 3,4-thiadiazol-2-yl]-5-nitro-2-furamide 392 44.7 210 (E)-3- (2-chlorophenyl)-N- [5- (phenethylamino)-1,3,4- thiadiazol-2-yl]-2-propenamide 385 44.6 211 (E)-N-(5-{[2-(ethylsulfanyl) ethyl] amino}-1,3,4-thiadiazol- 2-yl)-3-phenyl-2-propenamide 335 44.3 212 N-(5-{[3-(cyclohexylamino)propyl]amino}-1, 3,4-thiadiazol- 2-yl)-4-iodobenzamide 486 44.2 213 2-ethoxy-N- {5-[(2-furylmethyl) amino]-1, 3,4-thiadiazol-2- yl}-1-naphthamide 395 44.2 214 N- {5- [ (1-naphthylmethyl) amino]-1,3, 4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide--44.1 215 (E)-N-(5-{[2-(lH-imidazol-4-yl) ethyl] amino}-1,3,4-thiadiazol- 2-yl)-3-phenyl-2-propenamide 341 44.1 216 (E)-3- (2-chlorophenyl)-N- [5- (undecylamino)-1,3,4-thiadiazol- 43.92-yl]-2-propenamide- 217 4-[({5-[(3,3-diphenylpropyl)amino]-1,3,4-thiadiazol-2- yl} amino) carbonyllbenzenesulfonyl fluoride 497 43.9 218 L-2362 N-{5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4- thiadiazol-2-yl}-1-benzothiophene-2-carboxamide 450 43.6

219 N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol-2-yl)- 2,4,6-trüsopropylbenzamide 490 43.6 220 (E)-N-{5-[(2-morpholinoethyl) amino]-1,3,4-thiadiazol-2-yl}- 3-phenyl-2-propenamide 360 43.6 221 (E)-3-)2-chlorophenyl)-N-(5-{[3-(1H-imidazol-1-yl)propyl] amino}-1, 3,4-thiadiazol-2-yl)-2-propenamide 389 43.5 222 N- {5- [ (4-pyridinylmethyl) amino]-1,3, 4-thiadiazl-2-yl}-1- benzothiophene-2-carboxamide 368 43.2 223 N-(5-{[4-(aminosulfonyl)benzyl]amino}-1,3,4-thiadiazol-2- yl)-1-benzothiophene-2-carboxamide 446 43.1 224 N-{5-[(2- 2-diphenylethyl) amino]-1,3,4-thiadiazol-2-yl}-2- methoxybenzamide 431 43.0 225 4-thiadiazol- 2-yl} benzamide 421 42.9 226 N- {5- [ (3,3-diphenylpropyl) amino]-1,3,4-thiadiazol-2-yl}- 3-nitrobenzamide 460 42.9 227 N- [5- (cyclopropylamino)-1,3,4-thiadiazol-2-yl]-2-ethoxy-1- naphthamide 355 42.8 228 3,5-difluoro-N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 382 42.8 229 N\ (u) 2\ (d)-undecyl-1,3,4-thiadiazole-2,5-diamine 271 42.5 230 N- (5-{[4-(aminosulfonyl) phenethyl] amino}-1, 3,4-thiadiazol- 2-yl)-4-methylbenzamide 418 42.3 231 2-ethoxy-N-{5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2-yl}- 1-naphthamide 447 42.3 232 2,4,6-triisopropyl-N- {5-[(2-piperidinoethyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide 458 42.2 233 2-ethoxy-N- [5- (neopentylamino)-1,3,4-thiadiazol-2-yl]- 1-naphthamide 385 42.1 234 N- (5-{[2-(2-thienyl) ethyl] amino}-1, 3,4-thiadiazol-2-yl)-1- benzothiophene-2-carboxamide 387 42.0 235 N\ (u) 2\ (d)-(1-naphthylmethyl)-1,3,4-thiadiazole-2, 5-diamine 257 41.8 236 N-{5-[(2-anilinoethyl)amino]-1,3,4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide 396 41.6 237 N- {5-[(2-thienylmethyl) amino]-1, 3, 4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide 373 41.5

238 (E)-N-{5-[(2-furylmethyl) amino]-1, 3, 4-thiadiazol-2-yl}-9- octadecenamide 461 41.5 239 4- (trifluoromethyl)-N- [5- (undecylamino)-1,3,4-thiadiazol-2- yl] benzamide 443 41.4 240 (E)-3- (2-chlorophenyl)-N- {5- [ (3,3-diphenylpropyl) amino]- 1,3, 4-thiadiazol-2-yl}-2-propenamide - 41. 3 241 2,6-dichloro-N- {5-[(2-pyridinylmethyl) amino]-1, 3,4-thiadiazol- 2-yl} benzamide 380 41.3 242 2-ethoxy-N-(5{[3-(1H-imidazol-1-yl)propyl]amino}-1, 3,4- thiadiazol-2-yl)-1-naphthamide 423 41.3 243 N- {5- [ (3,3-diphenylpropyl) amino]-1, 3,4-thiadiazol-2-yl}- 2,4-difluorobenzamide 451 41.1 244 4-cyano-N- {5- [ (3,4-dimethoxybenzyl) amino]-1, 3,4-thiadiazol- 2-yl} benzamide 396 41.0 245 4-[({5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2- yl} amino) carbonyl] benzenesulfonyl fluoride 435 41.0 246 (E)-N-{5-[(tetrahydro-2-furanylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-9-octadecenamide 465 40.9 247 3,4-dichloro-N- {5-[(2-furylmethyl) amino]-1, 3,4-thiadiazol-2- yl} benzamide 369 40.9 248 N- {5-[(2-anilinoethyl) amino]-1, 6- triisopropylbenzamide 466 40.8 249 (E)-N-{5-[(2-cyanoethyl) amino]-1,3,4-thiadiazol-2-yl}- 9-octadecenamide 432 40.6 250 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-2,4,6- triisopropylbenzamide 443 40.5 251 (E)-3-(2-chlorophenyl)-N-{5-[(2-furylmethyl) amino]-1,3,4- thiadiazol-2-yl}-2-propenamide 361 40.3 252 N-(5-{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4-thiadiazol-2-yl)- 4-iodobenzamide 490 40.2 253 (E)-N-{5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4-thiadiazol-2- yl}-9-octadecenamide 554 40.1 254 5-chloro-N- (5-{[2-(phenylsulfanyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) pentanamide 371 40.0 255 2,6-dichloro-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 432 39.9

256 N-[5-(cycloheptylamino)-1, 3,4-thiadiazol-2-yl]-1-benzothiophene- 2-carboxamide 373 39.8 257 N- [5- (undecylamino)-1,3,4-thiadiazol-2-yl]-1-benzothiophene- 2-carboxamide---39.8 258 N- (5-{[2-(acetylamino) ethyl] amino}-1, 3,4-thiadiazol-2-yl)- 1,3-dioxo-l, 3-dihydro-2-benzofuran-5-carboxamide 376 39.7 259 N- (5-{[4-(aminosulfonyl) phenethyl] amino}-1, 3,4-thiadiazol-2- yl)-2,6-dichlorobenzamide 472 39.6 260 4- thiadiazol-2-yl} benzamide 479 39.6 261 N-[5-({[(2R)-6,6-dimethylbicylo[3.1.1]hept-2-yl]methyl}amino }- 1,3,4-thiadiazol-2-yl]-2-ethoxy-1-naphthamide 451 39.5 262 (E)-N- [5- (phenethylamino)-1,3,4-thiadiazol-2-yl]-3- phenyl-2-propenamide 351 39.5 263 3, 4-dichloro-N-{5-[(4-pyridinylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 380 39.4 264 N- 5- [ (2-anilinoethyl) ainino]-1,3,4-thiadiazol-2-yl}-5- nitro-2-furamide 375 39.2 265 N- {5- [ (1-benzyl-4-piperidinyl) amino]-1,3,4-thiadiazol- 2-yl}-2,4,6-triisopropylbenzamide 520 39.1 266 4- thiadiazol-2-yl} benzamide 438 38.8 267 N-(5-{[4-(aminosulfonyl)phenethyl]amino}- 1,3,4-thiadiazol-2-yl)-l-benzothiophene-2-carboxamide 460 38.7 268 (E)-3-(2-chlorophenyl)-N-(5-{[2-(1H-indol-3-yl)ethyl]amino}- 1,3,4-thiadiazol-2-yl)-2-propenamide--38.7 269 N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol-2-yl)-1- benzothiophene-2-carboxamide---38.5 270 2-ethoxy-N- [5- (phenethylamino)-1,3, 4-thiadiazol-2-yl]-1- naphthamide 419 38.4 271 N-(5-{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4-thiadiazol-2-yl)- 3-nitrobenzamide 409 38.4 272 4-bromo-N-(5-{[3-(1H-imidazol-1-yl)propyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide 409 38.2 273 N-{5-[(1,3-benzodioxol-5-ylmethyl)amino]-1, 3,4-thiadiazol- 2-yl}-4-bromobenzamide 435 38.1

274 (E)-N-[5-(cycloheptylamino)-1,3,4-thiadiazol-2-yl]-3- phenyl-2-propenamide 343 38.1 275 N-(5-{[3-(cyclohexylamino)propyl]amino]-1, 3,4-thiadiazol-2- yl)-3,5-difluorobenzamide 396 37.9 276 (E)-3- (2-chlorophenyl)-N- [5- (cyclobutylamino)-1,3,4- thiadiazol-2-yl]-2-propenamide 335 37.9 277 N-{5-[(3, 3-diphenylpropyl) amino]-1,3,4-thiadiazol-2- 37.9yl}-1-benzothiphene-2-carboxamide- 278 4- ({[5-(cycloheptylamino)-1, 3,4-thiadiazol-2-yl] amino} carbonyl) benzenesulfonyl fluoride 399 37.5 279 (E)-N- [5- (2, 3-dihydro-lH-inden-1-ylamino)-1,3,4- thiadiazol-2-yll-9-octadecenamide 497 37.4 280 amino]-1, 3,4- thiadiazol-2-yl} benzamide 439 37.3 281 N- 5- [ (3, 3-diphenylpropyl) amino]-1,3,4-thiadiazol-2-yl}- 3,5-difluorobenzamide 451 37.3 282 5-nitro-N- [5- (phenethylaniino)-1,3,4-thiadiazol-2-yl]-2- furamide 360 37.1 283 2,6-dichloro-N- {5-[(2-ethylhexyl) amino]-1, 3,4-thiadiazol-2- yl} benzamide 401 37.0 284 N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4-thiadiazol- 2-yl)-4-(trifluoromethyl) benzamide 432 36.7 285 (E)-N-{5-[(cyclohexylmethyl) amino]-1,3,4-thiadiazol-2-yl}-9- octadecenamide 477 36.7 286 (E)-N-{5-[(2-ethylhexyl) amino]-1,3,4-thiadiazol-2-yl}-9- octadecenamide 493 36.3 287 N- [5- (cyclopropylamino)-1,3, 4-thiadiazol-2-yl]-1- benzothiophene-2-carboxamide 317 36.2 288 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2- yl]-4-iodobenzamide 443 36.2 289 4-iodo-N-{5-[(4-pyridinylmethyl)amino]-1, 3,4-thiadiazol- 2-yl} benzamide 438 36.0 290 (E)-N- {5- [ (1-benzyl-4-piperidinyl) amino]-1,3,4-thiadiazol- 2-yl}-3-phenyl-2-propenamide 420 35.9 291 N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2-yl}-3- nitrobenzamide 385 35.7

292 2,6-dichloro-N- (5-{[2-(ethylsulfanyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 377 35.6 293 tert-butyl 3-[(5-{[(2-ethoxy-1-naphthyl) carbonyl] amino}- 1,3,4-thiadiazol-2-yl) aminolpropanoate 443 35.5 294 (E)-N-{5-[(2-anilinoethyl) amino]-1,3,4-thiadiazol-2-yl}- 3-(2-chlorophenyl)-2-propenamide 400 35.4 295 3,4-dichloro-N- (5-{[2-(lH-indol-3-yl) ethyllamino}-1, 3,4- thiadiazol-2-yl)benzamide-35.4 296 5-nitro-N-(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}-1, 3,4- thiadiazol-2-yl)-2-furamide 381 35.1 297 N- {5- [ (3,3-diphenylpropyl) amino]-1, 3,4-thiadiazol-2-yl}- 4-iodobenzamide--35.0 298 N- {5- [ (3,3-diphenylpropyl) amino]-1, 3,4-thiadiazol-2-yl}- 5-nitro-2-furamide 450 35.0 299 N- {5- [ (3,3-diphenylpropyl) amino]-1,3,4-thiadiazol-2- yl}-2,4,6-triisopropylbenzamide 541 34.9 300 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-3,5- difluorobenzamide 353 34.9 301 N- {5- [ (3-pyridinylmethyl) amino]-1,3,4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide 368 34.8 302 N-{5-[(4-fluorobenzyl)amino]-1, 3,4-thiadiazol-2-yl}-3- nitrobenzamide 374 34.8 303 N-(5-{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4-thiadiazol-2-yl)-2- methoxybenzamide 394 34.7 304 N-{5-[(cyclohexylmethyl)amino]-1, 3,4-thiadiazol-2-yl}-2- methoxybenzamide 347 34.6 305 N- {5- [ (1,3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-2, 4-difluorobenzamide 391 34.5 306 N-{5-[(2,2-diphenylethyl)amino]-1,3,4-thiadiazol-2- yl}-5-nitro-2-furamide 436 34.4 307 4-cyano-N-[5-({[2R)-6,6-dimethylbicyclo[3.1.1]hept-2- yl]methyl}amino)-1, 3,4-thiadiazol-2-yl] benzamide 382 34.2 308 4-thiadiazol-2- yl] benzamide 393 34.2 309 4-bromo-N- (5-{[2-(ethylsulfanyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 389 34.0

310 N-[5-(cycloheptylamino)-1, 3,4-thiadiazol-2-yl]-2- methoxybenzamide 347 34.0 311 N- (5-1 [4- (aminosulfonyl) benzyl] amino}-1, 3,4- thiadiazol-2-yl)-3,4-dichlorobenzamide 458 33.9 312 5-chloro-N-[5-({[(wR)-6,6-dimethylbicyclo [3.1. l] hept-2- yl] methyl} amino)-1,3,4-thiadiazol-2-yl] pentanamide 371 33.9 313 (E)-N- {5- [ (3,4-dichlorobenzyl) amino]-1, 3,4-thiadiazol-2- yl}-9-octadecenamide 539 33.9 314 N- [5- (cydobutylamino)-1,3, 4-thiadiazol-2-yl]-2-ethoxy-1- naphthamide 369 33.8 315 5-chloro-N-{5-[(cyclohexylmethyl)amino]-1, 3,4- thiadiazol-2-yl} pentanamide 331 33.8 316 5-chloro-N- [5- (cycloheptylamino)-1,3,4- thiadiazol-2-yl] pentanamide 331 33.6 317 N-(5-{[2-(1H-imidazol-4-yl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-2,4,6-triisopropylbenzamide 411 33.6 318 2-ethoxy-N- (5-{[2-(ethylsulfanyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl)-1-naphthamide 403 33.6 319 (E)-3- (2-chlorophenyl)-N- [5- (neopentylamino)-1, 3, 4- thiadiazol-2-yl]-2-propenamide 351 33.5 320 (E)-3-(2-chlorophenyl)-N-[5-({[(2R)6,6-dimethylbicyclo [3.1. 1]hept-2-yl]methyl}amino)-1, 3,4-thiadiazol-2-yl]-2- propenamide---33.5 321 5-chloro-N-{5-[(4-fluorobenzyl)amino]-1, 3,4-thiadiazol-2- yl} pentanamide 343 33.2 322 (E)-3-(2-chlorophenyl)-N-(5-{[2-(phenylsulfanyl) ethyl] amino}- 1,3,4-thiadiazol-2-yl)-2-propenamide---33.2 323 N- [5- (cycloheptylamino)-1,3,4-thiadiazol-2-yl]-4- methylbenzamide 331 33.0 324 N- (5-{[3-(lH-imidazol-1-yl) propyl] amino}-1, 3,4- thiadiazol-2-yl)-4-iodobenzamide 455 32.9 325 5-chloro-N-(5-{[3-(2-oxo-1-pyrrolidinyl) propyl] amino}- 1,3,4-thiadiazol-2-yl) pentanamide 360 32.8 326 (E)-N-{5-[(4-fluorobenzyl)aminol01, 3,4-thiadiazol-2-yl}-3- phenyl-2-propenamide 355 32.7 327 2-methoxy-N- [5- (phenethylamino)-1,3,4-thiadiazol-2-

yl] benzamide 355 32.5 328 N-(5-{[4-(aminosulfonyl)phenethyl]amino}-1, 3,4-thiadiazol- 2-yl)-2-ethoxy-1-naphthamide 498 32.4 329 (E)-N-{5-[(1-naphthylmethyl)amino]-1, 3,4-thiadiazol-2-yl}- 3-phenyl-2-propenamide 387 32.4 330 N-(5-{[2-(1H=imidazol-4-yl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-1-benzothiophene-2-carboxamide 371 32.2 331 (E)-N-{5-[(3,3-diphenylpropyl)amino]-1,3,4-thiadiazol- 2-yl}-3-phenyl-2-propenamide-32.1 332 N-(5-{[2-(acetylamino)ethyl]amino}-1,3,4-thiadiazol-2- yl)-2,4,6-triisopropylbenzamide 432 32.0 333 (E)-N-{5-[(3, 4-dichlorobenzyl) amino]-1,3,4-thiadiazol-2- yl}-3-phenyl-2-propenamide 405 31.9 334 2-methoxy-N-{5-[(1-naphthylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 391 31.8 335 N- (5-{[4-(aminosulfonyl) phenethyllamino}-1, 3,4- thiadiazol-2-yl)-4-cyanobenzamide 429 31.7 336 (E)-N-(5-{[4-(aminosulfonyl) phenethyl] amino}-1,3,4- thiadiazol-2-yl)-9-octadecenamide--31.6 337 3-nitro-N- (5-{[2-(2-thienyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 376 31.6 338 tert-butyl 3-({5-[(2, 6-dichlorobenzoyl) amino]-1,3,4- thiadiazol-2-yl} nmino) propanoate 417 31.6 339 N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2-yl}-4- iodobenzamide 466 31.5 340 3-[(5-{[(1,3-dioxo-1,3-dihydro-2-benzofuran-5- yl) carbonyl] amino}-1,3,4-thiadiazol-2-yl) amino] propanoate 419 31.5 341 N- {5-[(2-furylmethyl) amino]-1, 3,4-thiadiazol-2-yl}-4- iodobenzamide 427 31.3 342 (E)-3-phenyl-N- [5- (undecylamino)-1,3,4-thiadiazol-2-yl]-2- propenamide 401 31.2 343 N- [5- (1,2,3,4-tetrahydro-l-naphthalenylamino)-1,3,4- thiadiazol-2-yl]-1-benzothiophene-2-carboxamide 407 31.2 344 4-[(5-{[(E)-3-(2-chlorophenyl)-2-propenoyl]amino}- 1,3,4-thiadiazol-2-yl) amino] tetrahydro-1 (2H)- pyridinecarboxylate 436 31.1

345 4-cyano-N- [5- (phenethylamino)-1,3,4-thiadiazol-2- yl]benzamide 350 30.9 346 5-chloro-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) pentanamide 378 30.7 347 3-nitro-N- [5- (1,2,3,4-tetrahydro-l-naphthalenylamino)-1,3,4- thiadiazol-2-yl] benzamide 396 30.6 348 N-{5-[(4-fluorobenzyl)amino]-1, 3,4-thiadiazol-2-yl}-2- methoxybenzamide 359 30.4 349 N-{5-[(2-furylmethyl)amino]-1, 3,4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide 357 30.3 350 N- {5- [ (3,4-dichlorobenzyl) amino]-1, 3,4-thiadiazol-2- yl}-5-nitro-2-furamide 414 30.3 351 4-bromo-N-(5-{[2-(1H-indol-3-yl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide 444 30.3 352 (E)-3-(2-chloropheyl)-N-{5-[(4-pyridinylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-2-propenamide 372 30.2 353 (E)-3- (2-chlorophenyl)-N- [5- (cyclopropylamino)-1,3,4- thiadiazol-2-yll-2-propenamide 321 30.2 354 5-chloro-N- [5- (phenethylamino)-1,3,4-thiadiazol-2-yl] pentanamide 339 29.9 355 N-[5-(2,3-dihydro-1H-inden-1-ylamino)-1, 3,4-thiadiazol-2- yll-3-nitrobenzamide 382 29.8 356 4-methyl-N- {5- [ (4-phenylbutyl) amino]-1,3,4-thiadiazol-2- yl} benzamide 367 29.6 357 (E)-3-(2-chlorophenyl)-N-{5-[(4-phenylbutyl)amino]-1, 3,4- thiadiazol-2-yl}-2-propenamide---29.4 358 N-{5-[(1,3-benzodioxol-5-ylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-2,4,6-triisopropylbenzamide 481 29.3 359 4-methyl-N- [5- (phenethylamino)-1,3,4-thiadiazol-2- yllbenzamide 339 29.1 360 (E)-N-{5-[(cyclohexylmethyl)amino]-1, 3,4-thiadiazol-2- yl}-3-phenyl-2-propenamide 343 29.0 361 N-{5-[(4-fluorobenzyl)amino]-1,3,4-thidiazol-2-yl}-1- benzothiophene-2-carboxamide 385 28.8 362 4- thiadiazol-2-yl} benzamide 397 28.8

363 2, 4-difluoro-N-{5-[(1-naphthylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 397 28.8 364 4-cyano-N-15- [ (cyclohexylmethyl) amino]-1,3,4- thiadiazol-2-yl} benzamide 342 28.7 365 4-cyano-N-{5-[(2-thienylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 342 28.7 366 N-(5-{[4-(aminosulfonyl)phenethyl]amino}-1, 3,4- thiadiazol-2-yl)-2-methoxybenzamide 434 28.6 367 N-{5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4- thiadiazol-2-yl}-4-iodobenzamide 520 28.6 368 ethyl 4- ( {5- [ (l-benzothiophen-2-ylcarbonyl) aniino]- 1,3,4-thiadiazol-2-yl} amino) tetrahydro-1 (2H)- pyridinecarboxylate 432 28.5 369 4- thiadiazol-2-yl] benzamide 385 28.3 370 2, 6-dichloro-N-(5-{[2-(1-pyrrolidinyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide 386 28.3 371 4-{[(5-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}-1, 3,4- thiadiazol-2-yl) amino]carbonyl}benzenesulfonyl fluoride 428 28.1 372 N- {5- [ (1, 3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-3,5-difluorobenzamide 391 28.1 373 3, 5-difluoro-N-{5-[(4-phenylbutyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 389 28.1 374 (E)-3- (2-chlorophenyl)-N- [5- (1,2,3,4-tetrahydro-l- naphthalenylamino)-1,3, 4-thiadiazol-2-yl]-2-propenamide 411 28.1 375 4-thiadiazol-2- yl] benzamide 443 27.9 376 N-{5-[(3,3-diphenylpropyl)amino]-1,3,4-thiadiazol-2-yl}-4- (trifluoromethyl) benzamide 483 27.9 377 4-thiadiazol-2- yl] benzamide 393 27.8 378 (E)-N-(5-{[3-(1H-imidazol-1-yl)propyl]amino}-1, 3,4- thiadiazol-2-yl)-9-octadecenamide 489 27.8 379 (E)-N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2- yl}-3-phenyl-2-propenamide 366 27.5 380 N-{5-[(cyclohexylmethyl)amino]-1, 3,4-thiadiazol-2-

yl}-5-nitro-2-furamide 352 27.5 381 2,4,6-triisopropyl-N-(5-{[3-(2-oxo-1-pyrrolidinyl) propyl]- amino}-1, 3,4-thiadiazol-2-yl) benzamide 472 27.4 382 5-chloro-N-{5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2- yl} pentanamide 367 27.3 383 N-{5-[(3, 3-diphenylpropyl) amino]-1,3,4-thiadiazol-2- yl}-2-methoxybenzamide 445 27.3 384 4- thiadiazol-2-yl} benzamide 385 27.2 385 4-bromo-N-{5-[(2,2-diphenylethyl)amino]-1,3,4-thiadiazol-2- yl}benzamide-27.2 386 4-bromo-N- {5- [ (3,3-diphenylpropyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide--26.9 387 N- (5-{[3-(cyclohexylamino) propyl] amino}-1, 3,4- thiadiazol-2-yl)-2-methoxybenzamide 390 26.8 388 -butyl 3- ( {5- [ 4- thiadiazol-2-yl} amino) propanoate 475 26.6 389 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}- amino)-1,3,4-thiadiazol-2-yl]-3,5-difluorobenzamide 393 26.5 390 N-(5-{[4-(aminosulfonyl)phenethyl]amino}-1, 3,4- thiadiazol-2-yl)-5-chloropentanamide 418 26.3 391 (E)-N-(5-{[2-(lH-imidazol-4-yl) ethyl] amino}-1,3,4- thiadiazol-2-yl)-9-octadecenamide 475 26.2 392 4-thiadiazol-2- yllbenzamide 359 26.2 393 N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2-yl}-4- methylbenzamide 354 26.1 394 N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2-yl}-2- methoxybenzamide 370 26.0 395 4-methyl-N-(5-{[3-(2-oxo-1-pyrrolidinyl) propyllamino}- 1,3,4-thiadiazol-2-yl) benzamide 360 25.9 396 2,4,6-triisopropyl-N- (5-{[2-(2-thienyl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 457 25.9 397 (E)-3-(2-chlorophenyl)-N-(5-{[2-(1-pyrrolidinyl) ethyl]- amino}-1,3,4-thiadiazol-2-yl)-2-propenamide 378 25.9 398 N-(5-{[4-(aminosulfonyl)bezyl]amino}-1, 3,4-

thiadiazol-2-yl)-4-(trifluoromethyl)(trifluoromethyl) benzamide 458 25.9 399 2,4, 6-triisopropyl-N-{5-[(3-pyridinylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 438 25.8 400 (E)-N-(5-{[2-(acetylamino) ethyl] amino}-1,3,4-thiadiazol-2- yl)-3-phenyl-2-propenamide 332 25.8 401 N- {5- [ (4-Quorobenzyl) amino]-l, 6- triisopropylbenzamide 455 25.5 402 4-iodo-N-{5-[(1-naphthylmethyl)amino]-1, 3,4- 25.5thiadiazol-2-yl}benzamide--- 403 N-[5-({[(2R)-6,6-dimethylbicyclo [3.1. l] hept-2-yl] methyl}- amino)-1,3,4-thiadiazol-2-yl]-1-benzothiophene-2-carboxamide -25.3 404 N- [5- (2, 3-dihydro-lH-inden-1-ylamino)-1,3,4-thiadiazol-2- yl]-5-nitro-2-furamide 372 25.2 405 N-{5-[(tetrahydro-2-furanylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-1-benzothiophene-2-carboxamide 361 25.0 406 N-(5-{[2-(ethylsulfanyl)ethyl]amino}-1, 3,4-thiadiazol-2- yl)-4- (trifluoromethyl) benzamide 377 25.0 407 tert-butyl 3-[(5-{[4-(trifluoromethyl)benzoyl]amino}-1, 3,4- thiadiazol-2-yl) amino] propanoate 417 25.0 408 N-{5-[(2-anilinoethyl)amino]-1, 3,4-thiadiazol-2-yl}-3,4- dichlorobenzamide 408 24.9 409 N-{5-[(cyclohexylmethyl)amino]-1, 6- triisopropylbenzamide 443 24.9 410 4-thiadiazol-2- yl] benzamide 443 24.9 411 3-nitro-N- [5- (phenethylamino)-1,3,4-thiadiazol-2- yllbenzamide 370 24.8 412 N-(5-{[2-(acetylamino)ethyl]amino}-1, 3,4-thiadiazol-2- yl)-1-benzothiophene-2-carboxamide 362 24.7 413 3-nitro-N-[5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2- yl} benzamide 398 24.7 414 N- (5- [ (1, 3-benzodioxol-5-ylmethyl) amino]-1,3,4- thiadiazol-2-yl}-2-methoxybenzamide 385 24.7 415 4-iodo-N- [5- (phenethylamino)-1,3,4-thiadiazol-2-yl] benzamide 451 24.6 416 N-{5-[(3, 4-dichlorobenzyl) amino]-1,3,4-thiadiazol-2-yl}-2,4- difluorobenzamide 415 24.5

417 3, 4-dichloro-N-{5-[(3-pyridinylmethyl)amino]-1, 3,4- thiadiazol-2-yl} benzamide 380 24.4 418 4-thiadiazol-2- yljbenzamide 385 24.4 419 4-bromo-N-(5-{[3-(2-oxo-1-pyrrolidinyl) propyl] amino}- 1,3,4-thiadiazol-2-yl) benzamide 426 24.3 420 3-({5-[(3,4-dichlorobenzoyl)amino]-1,3,4- thiadiazol-2-yl} amino) propanoate 417 24.1 421 (E)-3-phenyl-N-{5-[(3-pyridinylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-2-propenamide 338 24.0 422 (E)-3-(2-chlorophenyl)-N-(5-{[3-(4-methylpiprazino)- propyl] amino}-1,3,4-thiadiazol-2-yl)-2-propenamide 421 24.0 423 2, 4-difluoro-N-{5-[(4-fluorobenzyl)amino]-1, 3,4- thiadiazol-2-yllbenzamide 365 23.8 424 2,4,6-triisopropyl-N- {5-[(2-thienylmethyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide 443 23.6 425 4-iodo-N- {5-[(2-thienylmethyl) amino]-1, 3,4-thiadiazol-2- yl} benzamide 443 23.5 426 3-[(5-{[(E)-3-(2-chlorophenyl)-2-propenoyl]- amino}-1,3,4-thiadiazol-2-yl) amino]propanoate 409 23.5 427 2,4-difluoro-N-(5-{[3-(2-oxo-1-pyrrolidinyl) propyll- amino}-1, 3,4-thiadiazol-2-yl) benzamide 382 23.4 428 2-methoxy-N- [5- ( 1,2,3,4-tetrahydro-1-naphthalenylamino)- 1,3,4-thiadiazol-2-yl] benzamide 381 23.3 429 2-methoxy-N-{5-[(4-phenylbutyl)amino]-1, 3,4-thiadiazol-2- yl} benzamide 383 23.2 430 4-iodo-N- (5-{[2-(2-thienyl) ethyl] amino}-1, 3,4-thiadiazol-2- yl) benzamide 457 23.1 431 N- {5-[(cyclohexylmethyl) amino]-1, 3,4-thiadiazol-2-yl}-2- ethoxy-1-naphthamide 411 23.1 432 (E)-3-phenyl-N-(5-{[2-(1-pyrrolidinyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl)-2-propenamide 344 23.0 433 N- {5-[(cyclohexylmethyl) amino]-1, 3,4-thiadiazol-2-yl}-2,4- difluorobenzamide 353 22.9 434 N- {5-[(2-anilinoethyl) amino]-1, 3,4-thiadiazol-2-yl}-4- bromobenzamide 420 22.8

435 N-{5-[(2-cyanoethyl)amino]-1, 6- triisopropylbenzamid 400 22.8 436 N-{5-=[(3,4-dimethoxybenzyl)amino]-1, 3,4-thiadiazol-2- yl}-3-nitrobenzamide 416 22.8 437 4-thiadiazol-2- yllbenzamide 361 22.7 438 N-15- [ (2-anilinoethyl) amino]-1,3,4-thiadiazol-2-yl}-2,6- dichlorobenzamide 408 22.6 439 (E)-3-(2-chlorophenyl)-N-{5-[(cyclohexylmethyl) amino]- 1,3,4-thiadiazol-2-yl}-2-propenamide 377 22.5 440 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]- methyl} amino)-1,3,4-thiadiazol-2-yl]-2,4,6- triisopropylbenzamide 483 22.5 441 4- thiadiazol-2-yl] benzamide 501 22.5 442 N-{5-[(2-furylmethyl)amino]-1, 6- triisopropylbenzamide 427 22.3 443 (E)-3-(2-chlorophenyl)-N-{5-[(1-naphthylmethyl)amino]-1,3,4- thiadiazol-2-yl}-2-propenamide--22.1 444 N-(5-{[2-(dimethylamino)ethyl]amino}-1, 3,4-thiadiazol-2- yl)-2,4,6-triisopropylbenzamide 418 21.9 445 2, 4-difluoro-N-(5-{[2-(2-thienyl)ethyl]amino}-1, 3,4- thiadiazol-2-yl) benzamide 367 21.9 446 N- (5-{[4-(aminosulfonyl) phenethyl] amino}-1, 3,4- thiadiazol-2-yl)-4-(trifluoromethyl)(trifluoromethyl) benzamide 472 21.8 447 3,4-dichloro-N-(5-{[2-(ethylsulfanyl)ethyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 377 21.6 448 2,6-dichloro-N-(5-{[2-(1H-imidazol-4-yl)ethyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 383 21.6 449 N- {5-[(cyclohexylmethyl) amino]-1, 3,4-thiadiazol-2-yl}-4- methylbenzamide 331 21.5 450 2-ethoxy-N- {5- [ (tetrahydro-2-furanylmethyl) ammo]-1,3,4- thiadiazol-2-yl}-1-naphthamide 399 21.4 451 4- thiadiazol-2-yl} benzamide 365 21.4 452 N- {5- [ (3,4-dichlorobenzyl) amino]-1,3,4-thiadiazol-2-

yl}-2-methoxybenzamide 409 21.3 453 N-{5-[(2-morpholinoethyl)amino]-1, 3,4-thiadiazol-2-yl}-1- benzothiophene-2-carboxamide 390 21.2 454 N- (5-{[2-(lH-imidazol-4-yl) ethyl] amino}-1, 3,4- thiadiazol-2-yl)-4-iodobenzamide 441 21.2 455 N-{5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4-thiadiazol-2- yl}-4-bromobenzamide 472 20.8 456 N- {5- [ (1-benzyl-4-piperidinyl) amino]-1,3,4-thiadiazol-2- yl}-5-nitro-2-furamide 429 20.8 457 4-methyl-N- {5-[(1-naphthylmethyl) amino]-1, 3,4- thiadiazol-2-yl} benzamide 375 20.7 458 3,5-difluoro-N- (5-{[2-(lH-indol-3-yl) ethyl] amino}-1, 3,4- thiadiazol-2-yl) benzamide 400 20.7 459 N-{5-[(1,3-benzodioxol-5-ylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-4-iodobenzamide 481 20.7 460 4-[({5-[(1-benzyl-4-piperidinyl)amino]-1, 3,4-thiadiazol-2- yl} amino) carbonyl] benzenesulfonyl fluoride 476 20.7 461 3, 4-dichloro-N-{5-[(2-ethylhexyl)amino]-1, 3,4-thiadiazol-2- yl} benzamide 401 20.6 462 N-{5-[(3, 4-dichlorobenzyl) amino]-1,3,4-thiadiazol-2-yl}-3- nitrobenzamide 424 20.5 463 N-(5-{[2-(acetylamino)ethyl]amino}-1, 3,4-thiadiazol-2- yl)-2-ethoxy-1-naphthamide 400 20.3 464 4-cyano-N- {5-[(2-morpholinoethyl) amino]-1, 3,4-thiadiazol-2- yl} benzamide 359 20.3 465 (E)-N- [5- (cyclopropylamino)-1,3,4-thiadiazol-2-yl]-3- phenyl-2-propenamide 287 20.2 466 N-(5-{[2-ethylsulfanyl)ethyl]amino}-1, 3,4-thiadiazol-2- yl)-1-benzothiophene-2-carboxamide 365 20.1 467 4-iodo-N-(5-{[3-(4-methylpiperazino)propyl]amino}- 1,3,4-thiadiazol-2-yl) benzamide 487 20.1 468 3,4-tetrahydro-l-naphthalenylamino)- 1,3,4-thiadiazol-2-yl] benzamide 387 20.1 469 N-{5-[(2-morpholinoethyl)amino]-1, 3,4-thiadiazol-2- yl}-3-nitrobenzamide 379 20.1 470 N-{5-[(cyclopropylmethyl)amino]-1, 3,4-thiadiazol-2-

yl}-4-iodobenzamide 401 20.0 471 N-{5-[(1,3-benzodioxol-5-ylmethyl)amino]-1, 3,4- thiadiazol-2-yl}-4-cyanobenzamide 380 20.0 472 4-({[5-(phenethylamino)-1, 3,4-thiadiazol-2-yl] amino}- carbonyl) benzenesulfonyl fluoride 407 20.0

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