Synthesis of naphthyl-, quinolin- and anthracenyl- analogues of clofibric acid as PPARα agonists.

PPAR is a ligand activated transcription factor belonging to the nuclear receptor subfamily, involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPAR activation is important in steatosis, inflammation and fibrosis in preclinical models of non-alcoholic fatty liver disease identifying a new potential therapeutic area. In this work, three series of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized. In an effort to obtain new compounds active as PPAR agonists, these molecules were evaluated for PPAR transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPAR; noteworthy, optically active naphthyl derivatives activated PPAR better than corresponding parent compound.