Substituted dihydropyrano indole-3,4-dione derivatives and 3-oxoacetic acid substituted 2-hydroxymethylindole derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

摘要

Substituted indole compounds of formula (I) are disclosed, wherein: X is an alkali metal or a basic amine moiety; R1 is H, C1-C8alkyl, C3-C6cycloalkyl, -CH2-cycloalkyl, pyridinyl, -CH2-pyridinyl, phenyl or benzyl, the rings of these groups being optionally substituted; R2 is H, halogen, C1-C6alkyl, C1-C3perfluoroalkyl, C1-C6alkoxy, C3-C6cycloalkyl, -CH2-C3-C6cycloalkyl, -NH2, or -NO2; R3 is H, halogen, C1-C6alkyl, C1-C3perfluoroalkyl, C1-C6alkoxy, C3-C6cycloalkyl, -CH2-C3-C6cycloalkyl, -NH2, or -NO2, phenyl, benzyl, benzyloxy, pyridinyl, or -CH2-pyridinyl, with the rings of these groups being optionally substituted; or a pharmaceutically acceptable salt or ester form thereof, as well as pharmaceutical compositions. These compounds are suitable as inhibitors of plasminogen activator inhibitor-1 (PAI-1) and as therapeutic compositions for treating conditions resulting from fibrinolytic disorders such as deep vein thrombosis and coronary heart disease, and pulmonary fibrosis.