Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARα antagonists

  • Bioorg Med Chem Lett. 2011 Aug 15;21(16):4869-72. doi: 10.1016/j.bmcl.2011.06.028.
Alessandra Ammazzalorso  1 ,  Antonella Giancristofaro ,  Alessandra D'Angelo ,  Barbara De Filippis ,  Marialuigia Fantacuzzi ,  Letizia Giampietro ,  Cristina Maccallini ,  Rosa Amoroso
Affiliations
  • 1. Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, Chieti, Italy.
PMID: 21742490 DOI: 10.1016/j.bmcl.2011.06.028
Abstract

The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPARα antagonists obtained from chemical modification of carboxylic acid agonists. In this work, a group of phenylsulfonamides were synthesized and in vitro evaluated against the agonistic effect of GW7647; they showed an inhibitory effect on PPARα activation, with best compounds revealing a dose-dependent antagonistic profile. Some of these antagonists showed also an inhibitory effect on CPT1A pattern expression.