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

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Thieme TM, Steri R, Proschak E, Paulke A, Schneider G, Schubert-Zsilavecz M

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. Epub 2010 Mar 4.

PubMed ID

20307981 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Pioglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	300	N/A	N/A	Details