Discovery of inhibitors of plasminogen activator inhibitor-1: Structure–activity study of 5-nitro-2-phenoxybenzoic acid derivatives

Two novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed as potent PAI-1 inhibitors using hybridization and conformational restriction strategy in the tiplaxtinin and piperazine chemo types. The lead compounds 5a, 6c, and 6e exhibited potent PAI-1 inhibitory activity and favorable oral bioavailability in the rodents.

Graphical abstractTwo novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed using hybridization and conformational restriction strategy in the known chemo types as potent and orally bioavailable PAI-1 inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide