Plasminogen activator inhibitor-1 inhibitor

摘要

The present invention provides a novel compound having plasminogen activator inhibitor-1 inhibitory activity, and an inhibitor of PAI-1 comprising the compound as an active ingredient. The present invention also provides a pharmaceutical composition having an inhibitory action on PAI-1 activity and being efficacious in the prevention and treatment of various diseases whose onset is associated with PAI-1 activity.

主权项

1. A compound represented by Formula (I) or a salt thereof: wherein R1 represents halogen, R2 represents hydrogen, halogen, C1-6-alkyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C3-8-cycloalkenyl, C2-6-alkynyl, C3-8-cycloalkyl-C2-6-alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; X represents —CH═CH—; A represents a group represented by the following Formula (II): wherein R3 and R4 are the same or different, and each represents hydrogen, substituted or unsubstituted C1-6-alkyl, or CF3;T represents a single bond;D represents substituted or unsubstituted aryl, heteroaryl except pyrazolyl, orbenzo-condensed heteroaryl; substituted or unsubstituted C4-8-cycloalkyl;substituted or unsubstituted C3-8-cycloalkenyl or heterocycloalkenyl; or adamantyl;q is 1 ; L represents a single bond; B is located at ortho position on the benzene ring to which imino is bound, and is COOR9 wherein R9 represents hydrogen; or a group converted to hydrogen in vivo, which is selected from the group consisting of C1-6-alkyl, aryl, aralkyl, —CH(R10)—O—CO—R11, —CH(R10)—O—CO—OR11, and a (5-alkyl-2-oxo-1,3-dioxolen-4-yl)methyl group represented by the following formula: wherein R10 is hydrogen or C1-6-alkyl, R11 is C1-6-alkyl or C3-8-cycloalkyl, and R12 is C1-6 alkyl; or a heterocyclic group represented by any of the following Formulae (XI)-(XIII): wherein Z represents oxygen or sulfur, provided that the following compounds and salts thereof are excluded: 2-[(biphenyl-4-ylcarbonyl)amino]-5-chlorobenzoic acid, and 5-chloro-2-({[4-(1H-pyrrol-1-yl)phenyl]carbonyl}amino)benzoic acid.