Patent ID: 6147085
Filing Date: 2000-11-14
Classification: A61P,C07D

Abstract:
A compound of the formula: ##STR57## or the pharmaceutically acceptable salts thereof wherein whereinAr is phenyl, mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, lower alkylamino, lower dialkylamino, carboxamido, N-lower alkyl carboxamido, N,N-lower dialkyl carboxamido, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 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;R.sup.1 is hydrogen, halogen, trifluoromethyl, C.sub.1 -C.sub.6 alkyl, or (C.sub.1 -C.sub.6 alkyl)-G.sup.1 --R.sup.2 where G.sup.1 is oxygen or sulfur and R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;W is C--R.sup.3 where R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl; andX is ##STR58## wherein V.sup.1 and V.sup.2 are CH.sub.2, CO, CS, SO.sub.2 or CH(C.sub.1 -C.sub.6 alkyl), with the proviso that both V.sup.1 and V.sup.2 cannot both be CO, CS or SO.sub.2 ;Y.sup.1 and Y.sup.2 independently represent a bond or C.sub.1 -C.sub.6 alkylene;A.sup.1 is NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are independently Hydrogen or a lower alkyl group, orA.sup.1 is C.sub.1 -C.sub.6 arylalkyl or C.sub.1 -C.sub.6 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- 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, orlower alkanoyl, lower alkylsulfonyl, with the proviso that R.sup.4 and R.sup.5 cannot both be alkanoyl or alkylsulfonyl; orA.sup.1 is NR.sup.4 R.sup.5 wherein R.sup.4 is hydrogen or a C.sub.1 -C.sub.6 alkyl group and R.sup.5 forms a heterocycloalkyl group with Y.sup.1 when Y.sup.1 is alkylene; orA.sup.1 is NR.sup.4 R.sup.5 wherein NR.sup.4 R.sup.5 is a C.sub.3 -C.sub.6 heterocycloalkyl, orA.sup.1 is NR.sup.4 R.sup.5 wherein NR.sup.4 R.sup.5 is a 5- or 6-membered nitrogen heterocycle optionally containing an oxygen or second nitrogen atom, orA.sup.1 is a group of the formula: ##STR59## wherein e and f are independently 1, 2 or 3 and the sum of e and f is at least 3; andG.sup.2 isNR.sup.6 wherein R.sup.6 is hydrogen or C.sub.1 -C.sub.6 alkyl, orCH(C.sub.0 -C.sub.6 alkylene)-G.sup.3 --R.sup.7 wherein G.sup.3 is CONH, CONH(C.sub.1 -C.sub.6 alkyl), NH, NH(C.sub.1 -C.sub.6 alkyl) and R.sup.7 is hydrogen or C.sub.1 -C.sub.6 alkyl; orCONH.sub.2, CO[N(C.sub.1 -C.sub.6 alkyl)R.sup.8 ] wherein R.sup.8 is hydrogen or C.sub.1 -C.sub.6 alkyl;C.sub.1 -C.sub.6 arylalkyl or C.sub.1 -C.sub.6 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;A.sup.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.6 alkylene)-G.sup.4 --R.sup.9 wherein G.sup.4 is oxygen or sulfur and R.sup.9 is hydrogen, trifluoromethyl or C.sub.1 -C.sub.6 alkyl; ##STR60## wherein heteroaryl is 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, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, with the proviso that tetrazolyl can have at most one substituent;Z.sup.1 is C.sub.1 -C.sub.6 alkyl; andV.sup.2, Y.sup.2 and A.sup.2 are as defined above; ##STR61## where Z.sup.2 is carbon or nitrogen;wherewhen Z.sup.2 is CH, n is 0, 1, 2 or 3 and p is 1, 2, or 3, R is carboxamido, or (C.sub.0 -C.sub.6 alkylene)-G -R wherein G5 is NH, NH(C.sub.1 -C.sub.6 alkyl) and R is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 arylalkyl or C.sub.1 -C.sub.6 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;when Z is carbon, n is 1 or 2 and p is 1 or 2, R.sup.10 is amino; orwhen Z.sup.2 is nitrogen, n is 1 or 2 and p is 1 or 2, R.sup.10 is hydrogen; or(iv) a nitrogen heterocycle of the formula: ##STR62## wherein the N-ring represents triazolyl, tetrazolyl, imidazolyl, or pyrazolyl, each of which is optionally substituted with amino, trifluoromethyl, carboxamido, or (C.sub.1 -C.sub.6 alkylene)-G.sup.6 --R.sup.12 wherein G.sup.6 is NH, NH(C.sub.1 -C.sub.6 alkyl) and R.sup.12 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 arylalkyl or C.sub.1 -C.sub.6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-, 3-, or 4-pyridyl, 2-, or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 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.