Patent ID: 6153609
Filing Date: 2000-11-28
Classification: A61P,C07C,C07D

Abstract:
A compound of the formula ##STR7## or the pharmaceutically acceptable salts thereof, wherein n is 1 to 6;X is OR.sup.1 wherein R.sup.1 is as defined below; azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, indolinyl, isoindolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, piperazinyl or a bridged diazabicycloalkyl ring selected from the group consisting of ##STR8## wherein r is 1, 2 or 3;m is 1 or 2; andp is 0 or 1;wherein each heterocyclic group may optionally be substituted by one or two groups selected from hydroxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.10)acyl, (C.sub.1 -C.sub.10)acyloxy, (C.sub.6 -C.sub.10)aryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl, C.sub.5 -C.sub.9)heteroaryl (C.sub.1 -C.sub.6)alkyl, hydroxy (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)acyloxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylthio (C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)arylthio, (C.sub.6 -C.sub.10)arylthio(C.sub.1 -C.sub.6)alkyl, R.sup.9 R.sup.10 N, R.sup.9 R.sup.10 NSO.sub.2, R.sup.9 R.sup.10 NCO, R.sup.9 R.sup.10 NCO(C.sub.1 -C.sub.6)alkyl wherein R.sup.9 and R.sup.10 are each independently hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryl, C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl (C.sub.1 -C.sub.6)alkyl or (C.sub.5 -C.sub.9)heteroaryl (C.sub.1 -C.sub.6)alkyl or R.sup.9 and R.sup.10 may be taken together with the nitrogen to which they are attached to form an azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl or thiomorpolinyl ring; R.sup.12 SO.sub.2, R.sup.12 SO.sub.2 NH wherein R.sup.12 is trifluoromethyl, (C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl or (C.sub.5 -C.sub.9)heteroaryl (C.sub.1 -C.sub.6)alkyl; R.sup.13 CONR.sup.9 wherein R.sup.9 is as defined above and R.sup.13 is hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.6 -C.sub.10)aryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.1 -C.sub.6)aryl(C.sub.1 -C.sub.6)alkyl(C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkoxy or (C.sub.5 -C.sub.9)heteroaryl(C.sub.1 -C.sub.6)alkyl; R.sup.14 OOC, R.sup.14 OOC(C.sub.1 -C.sub.6)alkyl wherein R.sup.14 is (C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl (C.sub.1 -C.sub.6)alkyl, 5-indanyl, CHR.sup.5 OCOR.sup.6 wherein R.sup.5 is hydrogen or (C.sub.1 -C.sub.6)alkyl and R.sup.6 is (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy or (C.sub.6 -C.sub.10)aryl; CH.sub.2 CONR.sup.7 R.sup.8 wherein R.sup.7 and R.sup.8 are each independently hydrogen or (C.sub.1 -C.sub.6)alkyl or may be taken together with the nitrogen to which they are attached to form an azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinyl ring; or R.sup.15 O (C.sub.1 C.sub.6)alkyl wherein R.sup.15 is H.sub.2 N(CHR.sup.16)CO wherein R.sup.16 is the side chain of a natural D- or L-amino acid;R.sup.1 is (C.sub.6 -C.sub.10)aryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl, 5-indanyl, CHR.sup.5 OCOR.sup.6 or CH.sub.2 CONR.sup.7 R.sup.8 wherein R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are as defined above;R.sup.3 and R.sup.4 are each independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl (difluoromethylene), (C.sub.1 -C.sub.3)alkyl(difluoromethylene)(C.sub.1 -C.sub.3)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl, (C.sub.5 -C.sub.9)heteroaryl(C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryl(C.sub.6 -C.sub.10)aryl, (C.sub.6 -C.sub.10)aryl(C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.6)cycloalkyl, (C.sub.3 -C.sub.6)cycloalkyl(C.sub.1 -C.sub.6)alkyl, hydroxy(C.sub.1 -C.sub.6)alkyl, C.sub.1 -C.sub.10)acyloxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.10)acylamino(C.sub.1 -C.sub.6)alkyl, piperidyl, (C.sub.1 -C.sub.6)alkylpiperidyl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.5 -C.sub.9)heteroaryl(C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylthio(C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)arylthio(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylsulfinyl(C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)arylsulfinyl(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylsulfonyl(C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)arylsulfonyl(C.sub.1 -C.sub.6)alkyl, amino(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylamino(C.sub.1 -C.sub.6)alkyl, ((C.sub.1 -C.sub.6)alkylamino.sub.2 (C.sub.1 -C.sub.6)alkyl, R.sup.17 CO(C.sub.1 -C.sub.6)alkyl wherein R.sup.17 is R.sup.14 O or R.sup.7 R.sup.8 N wherein R.sup.7, R.sup.8 and R.sup.14 are as defined above; or R.sup.18 (C.sub.1 -C.sub.6)alkyl wherein R.sup.18 is piperazinyl, (C.sub.1 -C.sub.10)acylpiperazinyl, (C.sub.6 -C.sub.10)arylpiperazinyl, (C.sub.5 -C.sub.9)heteroarylpiperazinyl, (C.sub.1 -C.sub.6)alkylpiperazinyl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkylpiperazinyl, (C.sub.5 -C.sub.9)heteroaryl(C.sub.1 -C.sub.6)alkylpiperazinyl, morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, piperidyl, (C.sub.1 -C.sub.6)alkylpiperidyl, (C.sub.6 -C.sub.10)arylpiperidyl, (C.sub.5 -C.sub.9)heteroarylpiperidyl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkylpiperidyl, (C.sub.5 -C.sub.9)heteroaryl(C.sub.1 -C.sub.6)alkylpiperidyl or (C.sub.1 -C.sub.10)acylpiperidyl;or R.sup.3 and R.sup.4 may be taken together to form a (C.sub.3 -C.sub.6)cycloalkyl, oxacyclohexyl, thiocyclohexyl, indanyl or tetralinyl ring or a group of the formula ##STR9## wherein R.sup.21 is hydrogen, (C.sub.1 -C.sub.10)acyl, (C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl, (C.sub.5 -C.sub.9)heteroaryl(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkylsulfonyl; andQ is (C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.6 -C.sub.10)aryloxy(C.sub.6 -C.sub.10)aryl, (C.sub.6 -C.sub.10)aryl(C.sub.6 -C.sub.10)aryl, (C.sub.6 -C.sub.10)aryl(C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkyl, (C.sub.6 -C.sub.10)aryloxy(C.sub.5 -C.sub.9)heteroaryl, (C.sub.5 -C.sub.9)heteroaryl, (C.sub.1 -C.sub.6)alkyl(C.sub.6 -C.sub.10)aryl, (C.sub.1 -C.sub.6)alkoxy(C.sub.6 -C.sub.10)aryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkoxy(C.sub.6 -C.sub.10)aryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.5 -C.sub.9)heteroaryloxy(C.sub.6 -C.sub.10)aryl, (C.sub.1 -C.sub.6)alkyl(C.sub.5 -C.sub.9)heteroaryl, (C.sub.1 -C.sub.6)alkoxy(C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryl(C.sub.1 -C.sub.6)alkoxy(C.sub.5 -C.sub.9)heteroaryl, (C.sub.5 -C.sub.9)heteroaryloxy(C.sub.5 -C.sub.9)heteroaryl, (C.sub.6 -C.sub.10)aryloxy(C.sub.1 -C.sub.6)alkyl, (C.sub.5 -C.sub.9)heteroaryloxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl(C.sub.6 -C.sub.10)aryloxy(C.sub.6 -C.sub.10)aryl, (C.sub.1 -C.sub.6)alkyl(C.sub.5 -C.sub.9)heteroaryloxy(C.sub.6 -C.sub.10)aryl, (C.sub.1 -C.sub.6)alkyl(C.sub.6 -C.sub.10)aryloxy(C.sub.5 -C.sub.9)heteroaryl, (C.sub.1 -C.sub.6)alkoxy(C.sub.6 -C.sub.10)aryloxy(C.sub.6 -C.sub.10)aryl, (C.sub.1 -C.sub.6)alkoxy(C.sub.5 -C.sub.9)heteroaryloxy(C.sub.6 -C.sub.10)aryl or (C.sub.1 -C.sub.6)alkoxy(C.sub.6 -C.sub.10)aryloxy(C.sub.5 -C.sub.9)heteroaryl wherein each aryl group is optionally substituted by fluoro, chloro, bromo, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy or perfluoro(C.sub.1 -C.sub.3)alkyl;with the proviso that X must be substituted when defined as azetidinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, indolinyl, isoindolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, piperazinyl, (C.sub.1 -C.sub.10)acylpiperazinyl, (C.sub.1 -C.sub.6)alkylpiperazinyl, (C.sub.6 -C.sub.10)arylpiperazinyl, (C.sub.5 -C.sub.9)heteroarylpiperazinyl or a bridged diazabicycloalkyl ring.