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.