4-(PHENYL-ETHYLIDENEAMINOXY-PROPOXY) -PHENYL-ACETIC ACID DERIVATIVES AND RELATED COMPOUNDS AS PAI-1 INHIBITORS FOR THE TREATMENT OF IMPAIRMENT OF THE FIBRINOLYTIC SYSTEM AND OF THROMBOSIS.

摘要

The present invention relates to substituted aryl oximes of formula (I) or a pharmaceutically acceptable salt or ester form thereof wherein R1 is a direct bond to A, C1-C4 alkylene, or -O-C1-C4 alkylene; R2 and R3 are , independently hydrogen, halogen, C1-C4 alkyl, C1-C3 perfluoroalkyl, -O-C1-C3 perfluoroalkyl, C1-C3 alkoxy, -OH, -NH2, -NO2, -O(CH2)p-aryl, -O(CH2)p-heteroaryl, aryl, heteroaryl, -NH(CH2)p-aryl, -NH(CH2)p-heteroaryl, -NH(CO)-aryl, -NH(CO)-heteroaryl, -O(CO)-aryl, -O(CO)-heteroaryl, -NH(CO)-CH=CH-aryl, or -NH(CO)-CH=CH-heteroaryl; p is an integer from 0-6; R4 is hydrogen, C1-C8 alkyl, or C3-C6 cycloalkyl; A is COOH or an acid mimic; X is C1-C8 alkylene, C3-C6 cycloalkylene, -(CH2)mO-, or -(CH2)mNH-; m is an integer from 1-6; R5 and R6 are, independently, hydrogen, halogen, C1-C6 alkyl, C1-C6 perfluoroalkyl, -O-C1-C6 perfluoroalkyl, C1-C6 alkoxy, -OH, -NH2, -NO2, -O(CH2)n-aryl, O(CH2)n-heteroaryl, aryl, or heteroaryl; and is an integer from 0-6, wherein C1-C4 alkaline, -O-C1-C4 alkaline, alkyl, aryl and heteroaryl are each optionally substituted by one or more substituents. The present compounds are PAI-1 inhibitors for the treatment e.g of impairment of the fibrinolytic system, thrombosis or cardiovascular diseases.