2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents

  • Bioorg Med Chem Lett. 2005 Jan 3;15(1):51-5. doi: 10.1016/j.bmcl.2004.10.042.
José A Martín  1 ,  Dawn A Brooks ,  Lourdes Prieto ,  Rosario González ,  Alicia Torrado ,  Isabel Rojo ,  Beatriz López de Uralde ,  Carlos Lamas ,  Rafael Ferritto ,  María Dolores Martín-Ortega ,  Javier Agejas ,  Francisco Parra ,  John R Rizzo ,  Gary A Rhodes ,  Roger L Robey ,  Charles A Alt ,  Samuel R Wendel ,  Tony Y Zhang ,  Anne Reifel-Miller ,  Chahrzad Montrose-Rafizadeh ,  Joseph T Brozinick ,  Eric Hawkins ,  Elizabeth A Misener ,  Daniel A Briere ,  Robert Ardecky ,  James D Fraser ,  Alan M Warshawsky
Affiliations
  • 1. Lilly Research Laboratories, Division of Eli Lilly & Company, Lilly S.A., Alcobendas 28108, Madrid, Spain. [email protected]
PMID: 15582409 DOI: 10.1016/j.bmcl.2004.10.042
Abstract

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.

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