4- (1-benzofuran-3-yl-methylideneaminoxy-propoxy) -benzoic acid derivatives and related compounds as inhibitors of pai-1 for the treatment of fibrinolytic system damage and thrombosis

摘要

"4- (1-BENZOFURAN-3-IL-METHYLIDENOAMINOXI-PROPoxy) -BENZ ACID DERIVATIVES AND RELATED COMPOUNDS AS PAI-1 INHIBITORS FOR FIBRINOLYTIC AND THROMBOSIS DAMAGE TREATMENT". The present invention relates to benzofuryl oximes of formula (I) or a pharmaceutically acceptable salt or ester form thereof, wherein R 1 is a direct bond to A, C 1 -C 4 alkylene, or -OC-1 -C-4-alkylene; R 2 and R 3 are independently hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 3 perfluoroalkyl, C 1 -C 3 perfluoroalkyl , C 1 -C 2 -C 3 alkoxy, -OH, -NH 2 C, -NO 2 C, aryl, heteroaryl, O (CH 2 C) aryl, aryl 2 ~) ~ p-heteroaryl, -NH (CH ~ 2 ~) ~ p-aryl, -NH (CH ~ 2 ~) ~ 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 to 6; R 4 is hydrogen, C 1 -C 8 alkyl, or C 3 -C 6 cycloalkyl; A is -COOH or an acid mimic; X is C 1 -C 8 alkylene, C 3 -C 6 cycloalkylene, - (CH 2 C) m - O, or (CH 2 C) -NH ; m is an integer from 1 to 6; and R5 is hydrogen, C1 -C8 alkyl, C3 -C6 cycloalkyl, CH2C3 cycloalkyl, heteroaryl, and CH 2 -heteroaryl, aryl, or benzyl; R 6 and R 7 are independently hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 perfluoroalkyl, OC 1 C 6 -C 6 perfluoroalkyl, C 1-1 -C 6 alkoxy, -OH, -NH ~ 2 ~, -NO ~ 2 ~, -O (CH ~ 2 ~) -N-aryl, -O (CH ~ 2 ~) n-heteroaryl, aryl, or heteroaryl; and n is an integer from 0 to 6, wherein the alkyl, cycloalkyl, aryl and heteroaryl groups are each optionally substituted by one or more substituents. The present compounds are PAI-1 inhibitors for the treatment for example of fibrinolytic system weakness, thrombosis or cardiovascular disease.