Identification of novel PPARα ligands by the structural modification of a PPARγ ligand

To develop novel PPARα ligands, we designed and synthesized several 3-{3-[2-(nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives. Compound 10, the meta isomer of a PPARγ agonist 1, has been identified as a PPARα ligand. The introduction of methyl and ethyl groups at the C-2 position of the propanoic acid of 10 further improved the PPARα-binding potency.

To develop novel PPARα ligands, we designed and synthesized several 3-{3-[2-(nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives which were designed based on the structure of PPARγ agonist 1. Among these compounds, compounds 10, 13 and 14 were found to be strong PPARα ligands.Figure optionsDownload as PowerPoint slide