2. Academic Validation
  3. Design and synthesis of novel and potent amide linked PPARgamma/delta dual agonists

Design and synthesis of novel and potent amide linked PPARgamma/delta dual agonists

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6744-9. doi: 10.1016/j.bmcl.2007.10.047.
Qing Shi 1,  Emily J Canada,  Yanping Xu,  Alan M Warshawsky,  Garret J Etgen,  Carol L Broderick,  Cathleen K Clutinger,  Lynnie A Irwin,  Michael E Laurila,  Chahrzad Montrose-Rafizadeh,  Brian A Oldham,  Minmin Wang,  Leonard L Winneroski,  Chaoyu Xie,  Jeremy S York,  Nathan P Yumibe,  Richard W Zink,  Nathan Mantlo
Affiliations

Affiliation

  • 1 Eli Lilly and Company, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285, USA. shi_qing@lilly.com
PMID: 18029178 DOI: 10.1016/j.bmcl.2007.10.047
Abstract

A series of potent amide linked PPARgamma/delta dual agonists (1a) has been discovered through rational design. In the ZDF rat model of type 2 diabetes, compound (R)-3-[4-(3-{1-[(5-chloro-1,3-dimethyl-1H-indole-2-carbonyl)-amino]-ethyl}-5-fluoro-phenoxy)-2-ethyl-phenyl]-propionic acid (42) from this series has demonstrated glucose lowering efficacy comparable to the marketed PPARgamma agonist rosiglitazone with less weight gain.

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