Patent ID: 6362186
Filing Date: 2002-03-26
Classification: A61P,C07D

Abstract:
A compound of the formula: or the pharmaceutically acceptable salts thereof whereinAr is phenyl, 1- or 2-naphthyl, 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, lower alkylamino, lower dialkylamino, carboxamido, N-lower alkyl carboxamido, N,N-lower dialkyl carboxamido, C1-C6 alkyl, C1-C6 alkoxy, with the proviso that at least one of the positions ortho or para to the point of attachment of Ar to the tricyclic ring system is substituted; R1 is hydrogen, halogen, trifluoromethyl, C1-C6 alkyl, or (C1-C6 alkyl)-G1â€”R2 where G1 is oxygen or sulfur and R2 is hydrogen or C1-C6 alkyl; and X is â€ƒwherein V1 and V2 are CH2, CO, CS, SO2 or CH(C1-C6 alkyl), with the proviso that both V1 and V2 cannot both be CO, CS or SO2; Y1 and Y2 independently represent a bond or C1-C6 alkylene; A1 is NR4R5 wherein R4 and R5 are independently hydrogen or a lower alkyl group, or A1 is NR4R5 wherein R4 is hydrogen or a C1-C6 alkyl group and R5 forms a heterocyloalkyl group with Y1 when Y1 is alkylene; or A1 is C1-C6 arylalkyl or C1-C6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, lower alkylamino, lower dialkylamino, lower alkylcarboxamido, lower alkyl, lower alkoxy, with the proviso that 2 adjacent substituents can together form a 5-7 fused cycloalkyl or heterocycloalkyl ring; or A1 is lower alkanoyl, lower alkylsulfonyl, with the proviso that R4 and R5 cannot both be alkanoyl or alkylsulfonyl; or A1 is NR4R5 taken together form a C3-C6 heterocycloalkyl or a group of the formula: â€ƒwherein e and f are independently 1, 2 or 3 and the sum of e and f is at least 3; and G2 is NR6 wherein R6 is hydrogen or C1-C6 alkyl, or CH(C0-C6 alkylene)-G3â€”R7 wherein G3 is CONH, CONH(C1-C6 alkyl), NH, or NH(C1-C6 alkyl), and R7 is hydrogen or C1-C6 alkyl; or CONH2, CO[N(C1-C6 alkyl)R8] wherein R8 is hydrogen or C1-C6 alkyl; C1-C6 arylalkyl or C1-C6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, lower alkylamino, lower dialkylamino, lower alkylcarboxamido, lower alkyl, lower alkoxy, with the proviso that 2 adjacent substituents can together form a 5-7 fused cycloalkyl or heterocycloalkyl ring; A2 is hydrogen, C1-C6 alkyl, (C1-C6 alkylene)-G4â€”R9 wherein G4 is oxygen or sulfur and R9 is hydrogen, trifluoromethyl or C1-C6 alkyl; â€ƒwherein heteroaryl is 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono- or disubstituted with halogen, trifluoromethyl, amino, C1-C6 alkyl, C1-C6 alkoxy, with the proviso that tetrazolyl can have at most one substituent; Z1 is C1-C6 alkyl; and V2, Y2 and A2 are as defined above; â€ƒwhere Z2 is CH, or nitrogen; where â€ƒwhen Z2 is CH, n is 0, 1, 2 or 3 and p is 1, 2, or 3, R10 is carboxamido, or (C0-C6 alkylene)-G5â€”R11 wherein G5 is NH, NH(C1-C6 alkyl) and R11 is hydrogen, C1-C6 alkyl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, lower alkylamino, lower dialkylamino, lower alkylcarboxamido, lower alkyl, lower alkoxy, with the proviso that 2 adjacent substituents can together form a 5-7 fused cycloalkyl or heterocycloalkyl ring; â€ƒwhen Z2 is carbon, n is 1 or 2 and p is 1 or 2, R10 is amino; or â€ƒwhen Z2 is nitrogen, n is 1 or 2 and p is 1 or 2, R10 is hydrogen; or (iv) a nitrogen heterocycle of the formula: wherein the N-ring represents triazolyl, tetrazolyl, imidazolyl, or pyrazolyl, each of which is optionally substituted with amino, trifluoromethyl, carboxamido, or (C1-C6 alkylene)-G6â€”R12 wherein G6 is NH, NH(C1-C6 alkyl) and R12 is hydrogen, C1-C6 alkyl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, lower alkylamino, lower dialkylamino, lower alkylcarboxamido, lower alkyl, lower alkoxy, with the proviso that 2 adjacent substituents can together form a 5-7 fused cycloalkyl or heterocycloalkyl ring.