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  • Title: Discovery of a novel series of peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes and dyslipidemia.
    Author: Liu K, Xu L, Berger JP, Macnaul KL, Zhou G, Doebber TW, Forrest MJ, Moller DE, Jones AB.
    Journal: J Med Chem; 2005 Apr 07; 48(7):2262-5. PubMed ID: 15801817.
    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.
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