Phenoxyacetic acids as PPARδ partial agonists: synthesis, optimization, and in vivo efficacy

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2345-50. doi: 10.1016/j.bmcl.2011.02.077. Epub 2011 Mar 15.

Abstract

A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.

MeSH terms

  • Acetates / chemical synthesis
  • Acetates / chemistry*
  • Acetates / pharmacokinetics
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Male
  • Mice
  • Microsomes, Liver / metabolism
  • PPAR delta / agonists*
  • PPAR delta / metabolism
  • Rats
  • Structure-Activity Relationship

Substances

  • Acetates
  • PPAR delta
  • phenoxyacetic acid