Pyridine-2-propanoic acids: Discovery of dual PPARalpha/gamma agonists as antidiabetic agents

  • Bioorg Med Chem Lett. 2006 Dec 1;16(23):6116-9. doi: 10.1016/j.bmcl.2006.08.105.
Paul S Humphries  1 ,  Jonathon V Almaden ,  Sandra J Barnum ,  Thomas J Carlson ,  Quyen-Quyen T Do ,  James D Fraser ,  Mary Hess ,  Young H Kim ,  Kathleen M Ogilvie ,  Shaoxian Sun
Affiliations
  • 1. Department of Diabetes Chemistry, Pfizer Global R&D, 10770 Science Center Drive, San Diego, CA 92121, USA. [email protected]
PMID: 16979341 DOI: 10.1016/j.bmcl.2006.08.105
Abstract

A series of novel pyridine-2-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compound (S)-13 was selected for further profiling.