Patent ID: 6242438
Filing Date: 2001-06-05
Classification: A61P,C07D

Abstract:
A compound of the formula: ##STR112##or a pharmaceutically acceptable salt thereof, whereinR is C.sub.3 -C.sub.7 cycloalkyl, aryl or C.sub.1 -C.sub.6 alkyl, said C.sub.1 -C.sub.6 alkyl being optionally substituted by fluoro, --COOH, --COO(C.sub.1 -C.sub.4) alkyl, C.sub.3 -C.sub.7 cycloalkyl, adamantyl, aryl or het.sup.1, and said C.sub.3 -C.sub.7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, fluoro, fluoro(C.sub.1 -C.sub.4) alkyl and fluoro(C.sub.1 -C.sub.4)alkoxy;A is CO or SO.sub.2 ;R is phenyl, benzyl, naphthyl, thienyl, benzothienyl or indolyl, each optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo and trifluoromethyl;R.sup.2 is --CO.sub.2 H, --CONR.sup.3 R.sup.4, --CONR.sup.5 (C.sub.3 -C.sub.7 cycloalkyl), --NR.sup.5 (C.sub.2 -C.sub.5 alkanoyl), --NR.sup.3 R.sup.4, --NR.sup.5 CONR.sup.5 R.sup.6, (C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl)R.sup.5 N--, (C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl).sub.2 N--, --NR.sup.5 COCF.sub.3, --NR.sup.5 SO.sub.2 CF.sub.3, --NR.sup.5 (SO.sub.2 C.sub.1 -C.sub.4 alkyl), --NR.sup.5 SO.sub.2 NR.sup.5 R.sup.6, --NR.sup.5 (SO.sub.2 aryl), --N(aryl)(SO.sub.2 C.sub.1 -C.sub.4 alkyl), --OR.sup.5, --O(C.sub.3 -C.sub.7 cycloalkyl), --SO.sub.2 NR.sup.5 R.sup.6, het.sup.3 or a group of the formula: ##STR113##R.sup.3 and R.sup.4 are each independently selected from H and C.sub.1 -C.sub.4 alkyl optionally substituted by hydroxy, C.sub.1 -C.sub.4 alkoxy, --S(O).sub.p (C.sub.1 -C.sub.4 alkyl), amino, --NH(C.sub.1 -C.sub.4 alkyl), --N(C.sub.1 -C.sub.4 alkyl).sub.2 or het.sup.2 ;R.sup.5 and R.sup.6 are each independently selected from H, C.sub.1 -C.sub.4 alkyl and C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl, said C.sub.1 -C.sub.4 alkyl and C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl being optionally substituted by fluoro;R.sup.7 is H, C.sub.1 -C.sub.4 alkyl, hydroxy, fluoro(C.sub.1 -C.sub.4)alkyl or phenyl, said phenyl being optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, fluoro(C.sub.1 -C.sub.4)alkyl, halo, C.sub.1 -C.sub.4 alkoxy and fluoro (C.sub.1 -C.sub.4)alkoxy;R.sup.8 is H, fluoro, hydroxy, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.5 alkanoyl or C.sub.2 -C.sub.5 alkanoyloxy;R.sup.9 is --NR.sup.5 R.sup.6, --NR.sup.5 COR.sup.5, --NR.sup.5 SO.sub.2 CF.sub.3, --NR.sup.5 (SO.sub.2 C.sub.1 -C.sub.4 alkyl), --NR.sup.5 SO.sub.2 NR.sup.5 R.sup.6, --NR.sup.5 COO(C.sub.1 -C.sub.4 alkyl), --NR.sup.5 CONR.sup.5 R.sup.6, --NR.sup.5 (SO.sub.2 morpholino), --NR.sup.5 (SO.sub.2 aryl), --N(aryl)(SO.sub.2 C.sub.1 -C.sub.4 alkyl) or a group of the formula: ##STR114##X is C.sub.1 -C.sub.4 alkylene;X.sup.1 is a direct link or C.sub.1 -C.sub.6 alkylene;X.sup.2 is a direct link, CO, SO.sub.2 or NR.sup.5 CO;W is methylene, CO, CH(OH), C(OH).sub.2, CH(C.sub.1 -C.sub.4 alkoxy), CHCO.sub.2 H, CHCO.sub.2 (C.sub.1 -C.sub.4 alkyl), CHCONR.sup.5 R.sup.6, CHF, CF.sub.2, CH(azetidin-1-yl), CH(pyrrolidin-1-yl), CH(piperidin-1-yl), CH(morpholino), CH(benzoxazol-2-yl), CHR.sup.9, O, S(O).sub.p, NR.sup.5, N(C.sub.3 -C.sub.7 cycloalkyl), NSO.sub.2 (C.sub.1 -C.sub.4 alkyl), NSO.sub.2 NR.sup.5 R.sup.6, NSO.sub.2 CF.sub.3, NSO.sub.2 (morpholino), NSO.sub.2 (aryl), ##STR115##NCONR.sup.5 R.sup.6, NCOR.sup.5, NCO(aryl) or NCO.sub.2 (C.sub.1 -C.sub.4 alkyl);W.sup.1 is methylene, CO, CH(OH), C(OH).sub.2, CH(C.sub.1 -C.sub.4 alkoxy), CHCO.sub.2 H, CHCO.sub.2 (C.sub.1 -C.sub.4 alkyl), CHCONR.sup.5 R.sup.6, CHF, CF.sub.2, CH(azetidin-1-yl), CH(pyrrolidin-1-yl), CH(piperidin-1-yl), CH(morpholino) or CHR.sup.9 ;W.sup.2 is W.sup.1, --CH.sub.2 W.sup.1 --, --CH.sub.2 WCH.sub.2 -- or --CH.sub.2 CH.sub.2 WCH.sub.2 --;m is 0, 1 or 2;n is 1 or 2 when W is other than methylene and is 0, 1 or 2 when W is methylene;p is 0, 1 or 2;q is 1 or 2;r is 1, 2,3 or 4;""aryl"", used in the definition of R, R.sup.2, R.sub.9 and W, means naphthyl or phenyl, each optionally substituted by C.sub.1 -C.sub.4 alkyl, halo, --OR.sup.5, fluoro(C.sub.1 -C.sub.4)alkyl, C.sub.2 -C.sub.5 alkanoyl, --CONR.sup.5 R.sup.6, --SO.sub.2 NR.sup.5 R.sup.6 or phenyl;""het.sup.1 "", used in the definition of R, means thienyl or a 5- or 6-membered ring heteroaryl group containing either 1 or 2 nitrogen heteroatoms or one nitrogen heteroatom and one oxygen or sulphur heteroatom, each optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, fluoro(C.sub.1 -C.sub.4 alkyl) and fluoro(C.sub.1 -C.sub.4 alkoxy);""het.sup.2 "", used in the definitions of R.sup.3 and R.sup.4, means a 4- to 7-membered ring, non-aromatic, heterocyclic group containing 1 or 2 heteroatoms each independently selected from nitrogen, oxygen and S(O).sub.p, said group being optionally C-substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and fluoro(C.sub.1 -C.sub.4)alkyl, and said ring nitrogen heteroatom optionally bearing a H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.5 alkanoyl, --CONR.sup.5 R.sup.6 or --SO.sub.2 NR.sup.5 R.sup.6 substituent;and ""het.sup.3 "", used in the definition of R.sup.2 means an optionally benzo-fused, N-linked, 5-membered ring heteroaryl group containing from 1 to 4 nitrogen heteroatoms, which is optionally substituted, including in the benzo-fused portion, by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, fluoro and fluoro(C.sub.1 -C.sub.4)alkyl.