2. Academic Validation
  3. Design and synthesis of dual peroxisome proliferator-activated receptors gamma and delta agonists as novel euglycemic agents with a reduced weight gain profile

Design and synthesis of dual peroxisome proliferator-activated receptors gamma and delta agonists as novel euglycemic agents with a reduced weight gain profile

  • J Med Chem. 2006 Sep 21;49(19):5649-52. doi: 10.1021/jm060617c.
Yanping Xu 1,  Garret J Etgen,  Carol L Broderick,  Emily Canada,  Isabel Gonzalez,  Jason Lamar,  Chahrzad Montrose-Rafizadeh,  Brian A Oldham,  John J Osborne,  Chaoyu Xie,  Qing Shi,  Leonard L Winneroski,  Jeremy York,  Nathan Yumibe,  Richard Zink,  Nathan Mantlo
Affiliations

Affiliation

  • 1 Lilly Research Laboratories, A Division of Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. xu_yanping@lilly.com
PMID: 16970391 DOI: 10.1021/jm060617c
Abstract

The design and synthesis of the dual Peroxisome Proliferator-activated Receptor (PPAR) gamma/delta agonist (R)-3-{4-[3-(4-chloro-2-phenoxy-phenoxy)-butoxy]-2-ethyl-phenyl}-propionic acid (20) for the treatment of type 2 diabetes and associated dyslipidemia is described. The compound possesses a potent dual hPPAR gamma/delta agonist profile (IC(50) = 19 nM/4 nM; EC(50) = 102 nM/6 nM for hPPARgamma and hPPARdelta, respectively). In preclinical models, the compound improves Insulin sensitivity and reverses diabetic hyperglycemia with less weight gain at a given level of glucose control relative to rosiglitazone.

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