Novel selective PPARδ agonists: Optimization of activity by modification of alkynylallylic moiety

Y-shaped molecules bearing alkynylallylic moieties were found to be potent and selective PPARδ activators. The alkynylallylic moiety was synthesized from alkyn-1-ols by hydroalumination followed by a cross-coupling reaction. Series of active compounds 6 were obtained by stepwise changing the structure of the known PPARpan agonist 5 into Y-shaped compounds. The most active and selective compound, 6f, had a PPARδ potency of 0.13 μM, which is 50-fold more potent than compound 5.

Selective PPARδ agonists, 6, were obtained by SAR study of structural changes of the PPARpan agonist 5.Figure optionsDownload as PowerPoint slide