SUBSTITUTED 8-ARYLQUINOLINE INHIBITORS OF PHOSPHODIESTERASE -4, A PHARMACEUTICAL COMPOSITION BASED THEREON (VARIANTS)

摘要

Novel substituted 8-arylquinolines represented by Formula (I), of a pharmaceutically acceptable salt thereof, wherein S1, S2 and S3 are independently H, -OH; halogen, -C1-C6alkyI, -NO2, -CN, or ûC1-C6alkoxy, wherein the alkyl and alkoxy groups are optionally substituted with 1-5 substituents; wherein each substituent is independently a halogen or OH; R1 is a H, OH, halogen, carbonyl, or -C1-C6alkyl, -cycloC3-C6alkyl, -C1-C6alkenyI, -C1-C6alkoxy, aryl-, heteroaryl, -CN, -heterocycloC3-C6alkyl, -amino, -C1-C6alkylainino, -(C1-C6alkyl)(C1-C6alkyl)amino, -C1-C6,alkyl(oxy)C1-C6alkyl, -C(O)NH(aryl), -C(O)NH(heteroaryl), -SOnNH(aryl), -SOnNH(heteroaryl), -SOnNH(C1-C6alkyl), -C(O)N(C0-C6alkyl) (C0-C6alkyl), -NH-SOn-(C1-C6alkyl), -SOn-(C1-C6alkyl), -(C1-C6alkyl)-O-C(CN)-dialkylamino, or -(C1-C6alkyl)-SOn-(C1-C6alkyl) group, wherein any of the groups is optionally substituted with 1-5 substituents; wherein each substituent is independently a halogen, -OH, -CN, -C1-C6alkyl, -cycloC3-C6alkyl, -Ñ(O)(heterocyclîC3-Ñ6alkyl), -C(O)-O-(C0-C6alkyl), -C(O)-aryloxy, -C1-C6alkoxy, -(C0-C6alkyloxy, (C0-C6alkyl)(C0-C6alkyl)amino, cycloalkyloxy, acyl, acyloxy, -ñoñlîÑ3-C6alkyl, heterocycloC3-C6alkyl, aryl, heteroaryl, carbonyl, carbamoyl, or ûSOn-(C1-C6alkyl); A is CH, C-ester, or C-R4; R2 and R3 independently is an aryl, heteroaryl, H, halogen, -CN, -C1-C6alkyl, heterocycloalkyl, -C1-C6alkoxy, carbonyl, carbamoyl, -C(O)OH, -(C1-C6alkyl)-SOn(C1-C6alkyI), -C(O)N(Co-C6aIkyl)(Co-C6alkyl), or -C1-C6alkylacylamino group, wherein any of the groups is optionally substituted with 1-5 substituents, wherein each substituent is independently an aryl, heteroaryl, halogen, -NO2, -C(O)OH, carbonyl, -CN, -C1-C6alkyl, -SOn-(C1-C6alkyl), -SOn-(àrol), aryloxy, -heteroaryloxy, C1-C6alkoxy, N-oxide, -C(O)-heterocycloC3-C6,alkyl, -NH-cycloC3-C6alkyl, amino, -OH, or -(C0-C6alkyl)(C0-C6alkyl)amino, -C(O)-N(C0-C6alkyl)(C0-C6alkyl) substituent group, wherein each substituent group independently is optionally substituted with -OH, C1-C6alkoxy, -C1-C6alkyl, -cycloÑ3-Ñ6alkol, aryloxy, -C(O)OH, -C(O)O(C1-C6alkyl), halogen, -NO2, -CN, -SOn-(C1-C6alkyl), or -C(O)-N(C0-C6alkyl)(C0-C6alkyl); one of R2 and R3 must be an aryl or heteroaryl, optionally substituted; when R; and R3 are both an aryl or heteroaryl, then R; and R3 may be optionally connected by a thio, oxy, or (C1-C4alkyl) bridge to form a fused three ring system; are PDE4 inhibitors.