Pyridine-3-propanoic acids: Discovery of dual PPARα/γ agonists as antidiabetic agents

A series of novel pyridine-3-propanoic acids was synthesized. A structure–activity relationship study of these compounds led to the identification of potent dual PPARα/γ agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compounds (S)-14 and (S)-19 were selected for further profiling.

Graphical abstractA novel series of potent dual PPARα/γ agonists was identified. SAR studies led to the identification of a multitude of compounds with varied isoform selectivity.Figure optionsDownload full-size imageDownload as PowerPoint slide