Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor (PAI-1)

摘要

This invention provides indole oxo-acetyl amino acetic acid derivatives which are useful as inhibitors of plasminogen activator inhibitor-1 (PAI-1) useful for treating fibrinolytic disorders, the compounds having the structure: wherein: R₁ is alkyl or optionally substituted cycloalkyl, -CH₂-cycloalkyl, pyridinyl, CH₂-pyridinyl, phenyl or benzyl; R₂ is hydrogen, alkyl, cycloalkyl, -CH₂-cycloalkyl, or perfluoroalkyl; R₃ is hydrogen, halo, alkyl, perfluoroalkyl, alkoxy, cycloalkyl, -CH₂-cycloalkyl, -NH₂, or -NO₂; R₄ is optionally substituted phenyl, benzyl, benzyloxy, pyridinyl, or -CH₂-pyridinyl; R₈ is hydrogen, alkyl, cycloalkyl, -CH₂-cycloalkyl, perfluoroalkyl, aryl, substituted aryl, alkyl-aryl, or substituted alkyl-aryl; R₉ is hydrogen, alkyl, hydroxyalkyl, 4-hydroxybenzyl, 3-indolylymethylene, 4-imidazolylmethylene, HSCH₂-, CH₃SCH₂CH₂-, H₂NC(-O)CH₂-, H₂NC(-O)CH₂CH₂-, HO₂CCH₂-, HO₂CCH₂CH₂-, H₂NCH₂CH₂CH₂CH₂-, H₂NC(-NH)NHCH₂CH₂CH₂-, or taken together with R₈ as -CH₂CH₂CH₂-; or a pharmaceutically acceptable salt or ester form thereof.