Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as peroxisome proliferator-activated receptor alpha agonists

  • J Med Chem. 2009 Oct 22;52(20):6224-32. doi: 10.1021/jm900878u.
Letizia Giampietro  1 ,  Alessandra Ammazzalorso ,  Antonella Giancristofaro ,  Fabio Lannutti ,  Giancarlo Bettoni ,  Barbara De Filippis ,  Marialuigia Fantacuzzi ,  Cristina Maccallini ,  Michele Petruzzelli ,  Annalisa Morgano ,  Antonio Moschetta ,  Rosa Amoroso
Affiliations
  • 1. Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, Chieti, Italy.
PMID: 19791744 DOI: 10.1021/jm900878u
Abstract

A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human Peroxisome Proliferator-activated Receptor alpha (PPARalpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor alpha were screened for activity against the PPARgamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.