Selective, potent PPARγ agonists with cyclopentenone core structure

A series of analogues of the PPARγ ligand 15-deoxy-Δ12,14-PGJ2 have been synthesized by functionalization of a 5-alkyl-4-hydroxycyclopentenone core structure obtained by Piancatelli rearrangement of precursor furylcarbinol. Transient transactivation assays indicate that analogues 18 and 20 are selective nanomolar agonists of PPARγ. This subtype selectivity is lost in derivatives (23, 24) with an alkynyl (oct-1-yn) chain at the C3 position, although the cyclopentenone derivative with cis relative configuration (23) showed greater affinity for PPARα.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide