Document Report Card

ID: ALA1143558

Journal: J Med Chem

Title: Discovery of a novel series of peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes and dyslipidemia.

Authors: Liu K, Xu L, Berger JP, Macnaul KL, Zhou G, Doebber TW, Forrest MJ, Moller DE, Jones AB.

Abstract: A series of 2-aryloxy-2-methyl-propionic acid compounds and related analogues were designed, synthesized, and evaluated for their PPAR agonist activities. 2-[(5,7-Dipropyl-3-trifluoromethyl)-benzisoxazol-6-yloxy]-2-methylpropionic acid (4) was identified as a PPARalpha/gamma dual agonist with relative PPARalpha selectivity and demonstrated potent efficacy in lowering both glucose and lipids in animal models without causing body weight gain. The PPARalpha activity of 4 appeared to have played a significant role in lowering glucose levels in db/db mice.

CiteXplore: 15801817

DOI: 10.1021/jm048993p