1. Academic Validation
  2. Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator

Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator

  • Bioorg Med Chem Lett. 2010 Apr 15;20(8):2469-73. doi: 10.1016/j.bmcl.2010.03.008.
Theresa M Thieme 1 Ramona Steri Ewgenij Proschak Alexander Paulke Gisbert Schneider Manfred Schubert-Zsilavecz
Affiliations

Affiliation

  • 1 Institute of Pharmaceutical Chemistry, ZAFES/LiFF/FIRST, Goethe-University Frankfurt, 60438 Frankfurt, Germany. schubert-zsilavecz@pharmchem.uni-frankfurt.de
Abstract

Peroxisome Proliferator-activated Receptor gamma (PPARgamma) is involved in glucose and lipid homeostasis. PPARgamma agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPARgamma modulators (SPPARgammaMs) was developed, which are believed to show less side effects than full PPARgamma agonists. We have previously shown that alpha-substitution of pirinixic acid, a moderate agonist of PPARalpha and PPARgamma, leads to low micromolar active balanced dual agonists of PPARalpha and PPARgamma. Herein we present modifications of pirinixic acid leading to subtype-selective PPARgamma agonists and furthermore the development of a selective PPARgamma modulator guided by molecular docking studies.

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