Design, synthesis, and structural analysis of phenylpropanoic acid-type PPARγ-selective agonists: discovery of reversed stereochemistry-activity relationship

J Med Chem. 2011 Jan 13;54(1):331-41. doi: 10.1021/jm101233f. Epub 2010 Dec 3.


Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and computational studies of α-benzylphenylpropanoic acid PPARγ agonists. Interestingly, these compounds show a reversal of the stereochemistry-transactivation activity relationship observed with other phenylpropanoic acid ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Drug Design
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • PPAR gamma / agonists*
  • PPAR gamma / chemistry
  • PPAR gamma / genetics
  • Phenylpropionates / chemical synthesis*
  • Phenylpropionates / chemistry
  • Phenylpropionates / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transcriptional Activation


  • PPAR gamma
  • Phenylpropionates

Associated data

  • PDB/3AN3
  • PDB/3AN4