Patent ID: 6110936
Filing Date: 2000-08-29
Classification: A61P,C07D

Abstract:
A compound of the formula (I): ##STR21## wherein R.sup.1 is hydroxy or of the formula --NHC((.dbd.O)(1-4C)alkyl or --NHS(O).sub.n (1-4C)alkyl wherein n is 0, 1 or2;R.sup.2 and R.sup.3 are independently hydrogen or fluoro;R.sup.4 and R.sup.5 are independently hydrogen or methyl >A--B-- is of the formula >C.dbd.CH--, >CHCH.sub.2 --, or >C(OH)CH.sub.2 -- (> represents two single bonds);D is NR.sup.7 ;R.sup.7 is hydrogen, cyano, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl, AR (as defined hereinbelow) or a tetrazole ring system (optionally mono-substituted in the 1- or 2-position of the tetrazole ring) wherein the tetrazole ring system is joined to the nitrogen in NR.sup.7 by a ring carbon atom;or R.sup.7 is of the formula R.sup.10 CO--, R.sup.10 SO.sub.2 -- or R.sup.10 CS--wherein R.sup.10 is AR (as defined hereinbelow), cyclopentyl or cyclohexyl (wherein the last two-mentioned cycloalkyl rings are optionally mono-- or disubstituted by substituents independently selected from (1-4C)alkyl (including geminal disubstitution), hydroxy, (1-4C)alkoxy, (1-4C)alkylthio, acetamido, (1-4C)alkanoyl, cyano and trifluoromethyl), (1-4C)alkoxycarbonyl, hydrogen, amino, trifluoromethyl, (1-4C)alkylamino, di((1-4C)alkyl)amino, 2,3-dihydro-5-oxothiazolo-[3,2-A]pyrimidin-6-yl, 2-(2-furyl)ethenyl, 2-(2-thienyl)ethenyl, 2-phenylethenyl (wherein the phenyl substituent is optionally substituted by up to three substituents independently selected from (1-4C)alkoxy, halo and cyano), 3,4-dihydropyran-2-yl, coumal-5-yl, 5-methoxy-4-oxopyran-2-yl, N-acetylpyrrolidin-2-yl, 5-oxo-tetrahydrofuran-2-yl, benzopyranone or (1-10C)alkyl {wherein (1-10C)alkyl is optionally substituted by hydroxy, cyano, halo, (1-10C)alkoxy, benzyloxy, trifluoromethyl, (1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxy, (1-6C)alkanoyl, (1-4C)alkoxycarbonyl, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(2-6C)alkanoylamino, (1-4C)alkylS(O).sub.p NH--, ((1-4C)alkylS(O).sub.p ((1-4C)alkyl)NH--, fluoro(1-4C)alkylS(O).sub.p NH--, fluoro(1-4C)alkylS(O).sub.p ((1-4C)alkyl)NH--, phosphono, (1-4C)alkoxy(hydroxy)phosphoryl, di-(1-4C)alkoxyphosphoryl, (1-4C)alkylS(O).sub.q --, phenylS(O).sub.q -- (wherein the phenyl group is optionally substituted by up to three substituents independently selected from (1-4C)alkoxy, halo and cyano), or CY (as defined hereinbelow), wherein p is 1 or 2 and q is 0, 1 or 2};or R.sup.10 is of the formula R.sup.11 C(O)O(1-6C)alkyl wherein R.sup.11 is an optionally substituted furan, optionally substituted pyrrole, optionally substituted pyrazole, optionally substituted imidazole, optionally substituted triazole, optionally substituted pyrimidine, optionally substituted optionally substituted pyridazine, optionally substituted pyridine, optionally substituted isoxazole, optionally substituted oxazole, optionally substituted isothiazole, optionally substituted thiazole, optionally substituted thiophene, optionally substituted phenyl, (1-4C)alkylamino, benzyloxy-(1-4C)alkyl or optionally substituted (1-10C)alkyl;or R.sup.10 is of the formula R.sup.12 O-- wherein R.sup.12 is optionally substituted (1-6C)alkyl;or R.sup.7 is of the formula R.sup.a OC(R.sup.b).dbd.CH(C.dbd.O)--, R.sup.c C(.dbd.O)C(.dbd.O)--, R.sup.d N.dbd.C(R.sup.e)C(.dbd.O)-- or R.sup.f NHC(R.sup.8).dbd.CHC(.dbd.O)-- wherein R.sup.a is (1-6C)alkyl, R.sup.b is hydrogen or (1-6C)alkyl, or R.sup.a and R.sup.b together form a (3-4C)alkylene chain, R.sup.c is hydrogen, (1-6C)alkyl, hydroxy(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (1-6C)alkoxy, (1-6C)alkoxy(1-6C)alkoxy,(1-6C)alkoxy, hydroxy(2-6C)alkoxy, (1-4C)alkylamino(2-6C)alkoxy, di-(1-4C)alkylamino(2-6C)alkoxy, R.sup.d is (1-6C)alkyl, hydroxy or (1-6C)alkoxy, R.sup.e is hydrogen or (1-6C)alkyl, R.sup.f is hydrogen, (1-6C)alkyl, optionally substituted phenyl or an optionally substituted is an optionally substituted furan, optionally substituted pyrrole, optionally substituted pyrazole, optionally substituted imidazole, optionally substituted triazole, optionally substituted pyrimidine, optionally substituted pyridazine, optionally substituted pyridine, optionally substituted isoxazole, optionally substituted oxazole, optionally substituted isothiazole, optionally substituted thiazole, or optionally substituted thiophene, and R.sup.8 is hydrogen or (1-6C)alkyl;or R.sup.7 is of the formula R.sup.14 CH(R.sup.13) (CH.sub.2).sub.m -- wherein m is 0 or 1, R.sup.13 is fluoro, cyano, (1-4C)alkoxy, (1-4C)alkylsulfonyl, (1-4C)alkoxycarbonyl or hydroxy, (provided that when m is 0, R.sup.13 is not fluoro or hydroxy) and R.sup.14 is hydrogen or (1-4C)alkyl;wherein AR is optionally substituted phenyl, optionally substituted phenyl(1-4C)alkyl, optionally substituted furan, optionally substituted pyrrole, optionally substituted pyrazole, optionally substituted imidazole, optionally substituted triazole, optionally substituted pyrimidine, optionally substituted pyridazine, optionally substituted pyridine, optionally substituted isoxazole, optionally substituted oxazole, optionally substituted isothiazole, optionally substituted thiazole, optionally substituted thiophene, optionally substituted naphthyl, optionally substituted indole, optionally substituted benzofuran, optionally substituted benzoimidazole, optionally substituted benzothiophene, optionally substituted benzoisothiazole, optionally substituted benzoxazole, optionally substituted benzisoxazole, optionally substituted pyridoimidazole, optionally substituted pyrimidoimidazole, optionally substituted quinoline, optionally substituted quinoxaline, optionally substituted quinazoline, optionally substituted phthalazine, optionally substituted cinnoline, or optionally substituted naphthyridine, in which the bicyclic heteroaryl ring systems may be linked via an atom in either of the rings comprising the bicyclic system, and wherein the mono- and bicyclic heteroaryl ring systems are linked via a ring carbon atom;wherein CY is a 4-, 5- or 6-membered cycloalkyl ring, a 5- or 6-membered cycloalkenyl ring, naphthoxy, thiophen-2-yl, indol-1-yl, indol-3-yl, pyrimidin-2-ylthio, 1,4-benzodioxan-6-yl, sulfolan-3-yl, pyridin-2-yl; wherein any of the afore-mentioned ring systems in CY may be optionally substituted by up to three substituents independently selected from halo, (1-4C)alkyl (including geminal disubstitution when CY is a cycloalkyl or cycloalkenyl ring), acyl, oxo and nitro-(1-4C)alkyl;>X--Y-- is of the formula >C.dbd.CH-- or >CHCH.sub.2 --;and pharmaceutically-acceptable salts thereof.