Patent ID: 6271383
Filing Date: 2001-08-07
Classification: A61P,C07D

Abstract:
A compound of formula (I): ##STR22##whereinR.sup.1 is OH;R.sup.2 and R.sup.3 are each independently hydrogen or fluoro;R.sup.4 and R.sup.5 are each independently hydrogen, C.sub.1-4 alkyl, carboxy, C.sub.1-4 alkoxycarbonyl or independently R.sup.7 ;R.sup.6 is hydrogen, C.sub.1-4 alkyl, hydroxy, C.sub.1-4 alkoxy, or C.sub.2-4 alkanoylalkoxy;D is NR.sup.7 ;R.sup.7 is hydrogen, cyano, 2-(C.sub.1-4 alkoxycarbonyl)ethenyl, 2-cyanoethenyl, 2-cyano-2-(C.sub.1-4 alkyl)ethenyl, 2-(C.sub.1-4 alkylaminocarbonyl)ethenyl, AR or a tretrazole 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; orR.sup.7 is R.sup.10 C(.dbd.O)--, R.sup.10 SO.sub.2 -- or R.sup.10 C(.dbd.S)--; orR.sup.7 is R.sup.d OC(R.sup.e).dbd.CHC(.dbd.O)--, R.sup.f C(.dbd.O)C(.dbd.O)--, R.sup.g N.dbd.C(R.sup.h)C(.dbd.O)-- or R.sup.i NHC(R.sup.j).dbd.CHC(.dbd.O)--; orR.sup.7 is R.sup.14 CH(R.sup.13)(CH.sub.2).sub.m --;R.sup.10 is AR, cyclopentyl or cyclohexyl, wherein the last two mentioned cycloalkyl rings are optionally mono- or di-substituted by substituents selected from C.sub.1-4 alkyl, hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, acetamido, C.sub.1-4 alkanoyl, cyano and trifluoromethyl; orR.sup.10 is C.sub.1-4 alkoxycarbonyl, hydrogen, amino, C.sub.1-4 alkylamino, diC.sub.1-4 alkalkylamino, 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 C.sub.1-4 alkoxy, halo or cyano; orR.sup.10 is 3,4-dihydropyran-2-yl, coumal-5-yl, 5-methoxy-4-oxopyran-2-yl, N-acetylpyrrolidin-2-yl, 5-oxotetrahydrofuran-2-yl, benzopyranone or C.sub.1-10 alkyl, wherein C.sub.1-10 alkyl is optionally substituted by hydroxy, cyano, halo, C.sub.1-10 alkoxy, trifluoromethyl, C.sub.1-4 alkoxy-C.sub.1-4 alkoxy, C.sub.1-4 alkoxy-C.sub.1-4 alkoxy-C.sub.1-4 alkoxy, C.sub.1-4 alkanoyl, C.sub.1-4 alkoxycarbonyl, amino, C.sub.1-4 alkylamino, diC.sub.1-4 alkylamino, C.sub.1-6 alkanoylamino, C.sub.1-4 alkoxycarbonylamino, N--C.sub.1-4 alkoyl-N--C.sub.2-6 alkanoylamino, C.sub.1-4 alkylS(.dbd.O).sub.p NH--, C.sub.1-4 alkS(.dbd.O).sub.p (C.sub.1-4 alkyl)N--, fluoroC.sub.1-4 alkylS(.dbd.O).sub.p NH--, fluoroC.sub.1-4 alkS(.dbd.O).sub.p (C.sub.1-4 alkyl)N--, phosphono, C.sub.1-4 alkoxy(hydroxy)phosphoryl, diC.sub.1-4 alkoxyphosphoryl, C.sub.1-4 alkylS(.dbd.O).sub.q --, CY or phenylS(.dbd.O).sub.q --, wherein the phenyl group is optionally substituted by up to three substituents independently selected from C.sub.1-4 alkoxy, halo and cyano; orR.sup.10 is R.sup.11 C(.dbd.O)OC.sub.1-6 alkyl or R.sup.12 O--;R.sup.11 is an optionally substituted 5- or 6-membered heteroaryl, optionally substituted phenyl, C.sub.1-4 alkylamino, benyloxyC.sub.1-4 alkalkyl, or optionally substituted C.sub.1-10 alkyl;R.sup.12 is optionally substituted C.sub.1-6 alkyl;R.sup.13 is fluoro, cyano, C.sub.1-4 alkoxy, C.sub.1-4 alkylsulfonyl, C.sub.1-4 alkoxycarbonyl or hydroxy, provided that when m is 0, R.sup.13 is not fluoro or hydroxy;R.sup.14 is hydrogen or C.sub.1-4 alkyl;>A--B is of the formula >C.dbd.C(R.sup.a)--, >CHCHR.sup.a -- or >C(OH)CHR.sup.a ;> represents two single bondsR.sup.a is hydrogen or C.sub.1-4 alkyl;R.sup.d is C.sub.1-6 alkyl;R.sup.e is hydrogen or C.sub.1-6 alkyl; or Rd and Re together form a C.sub.3-4 alkylene chain;R.sup.f is hydrogen, C.sub.1-6 alkyl, hydroxylC.sub.1-6 alkyl, C.sub.1-6 alkoxyC.sub.1-6 alkyl, amino, C.sub.1-4 alkylamino, diC.sub.1-4 alkylamino, C.sub.1-6 alkoxy, C.sub.1-6 alkoxyC.sub.1-6 alkoxy, hydroxyC.sub.2-6 alkoxy, C.sub.1-4 alkylaminoC.sub.2-6 alkoxy or diC.sub.1-4 alkylaminoC.sub.2-6 alkoxy;R.sup.g is C.sub.1-6 alkyl, hydroxy, or C.sub.1-6 alkoxy;R.sup.h is hydrogen or C.sub.1-6 alkyl;R.sup.i is hydrogen, C.sub.1-6 alkyl, optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl;R.sup.j is hydrogen or C.sub.1-6 alkyl;AR is optionally substituted phenyl, optionally substituted phenylC.sub.1-4 alkyl, optionally substituted 5- or 6-membered heteroaryl, optionally substituted naphthyl or an optionally substituted 5/6 or 6/6 bicyclic heteroaryl ring system, 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;CY is 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-benxoioxan-6-yl, sulfolan-3-yl or pyridin-2-yl, wherein any of the aforementioned ring systems in CY may be optionally substituted by up to three substituents independently selected from halo, C.sub.1-4 alkyl, acyl, oxo and nitroC.sub.1-4 alkyl,m is 0 or 1;p is 1 or 2; andq is 0, 1, or 2; ora pharmaceutically acceptable salt thereof.