PYRROLIDINE DERIVATIVES HAVING PHOSPOLIPASE A2 INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME

摘要

SUMMARY OF THE INVENTION The present invention relates to phospholipase A2 inhibitors having the general formula (I) wherein R 1 is preferably hydrogen, alkyl, optionally substituted aryl or aralkyl or heteroaryl; Z is sulfur or oxygen, sulfinyl or optionally substituted imino, -CONH, -OCH-, or -CONHCH2-; X1 is carbonyl, alkylene or alkenylene, -CONH-, -CH2NHSO2-, -CH2NHCO-, -CH2NHCS-, -CH2O-, -OCH2- or CH2OCH2-; X 2 is an arylene group, an indoldyl group or a valence line; X3 is an alkylene or alkenylene group or a bond; A, B and E are oxygen or sulfur; D is hydrogen or hydroxyalkyl; Y1 - (CH2) mCO-, - (CH2) mCONH-, - (CH2) mCSNH-, - (CH2) mSO2-, - (CH2) mCOO-, - (CH2) nNHCO- or - (CH2) nNHSO2- general wherein m is 0-3 and n is 1-3 or valence; Y 2 is a group of formula (a), (b) or (c) wherein R 2 and R 3 are hydrogen or one of aryl, heteroaryl or cycloalkyl and the other is hydrogen or alkyl; R4, R5 and G, J and L are optionally substituted aromatic or heteroaromatic compounds or cycloalkanes; HE