Design, synthesis, and structure–activity relationships of piperidine and dehydropiperidine carboxylic acids as novel, potent dual PPARα/γ agonists

Several series of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs have been designed and synthesized as novel, potent dual PPARα/γ agonists. The SAR of these series of analogs is discussed. A rare double bond migration occurred during the basic hydrolysis of the α,β-unsaturated dehydropiperidine esters 12, and the structures of the migration products were confirmed through a series of 2D NMR experiments.

Graphical abstractThe SAR of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs as novel, potent dual PPARα/γ agonists is discussed. A rare double bond migration in dehydropiperidine series has been observed and discussed.Figure optionsDownload full-size imageDownload as PowerPoint slide