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.
Masao Ohashi  1 ,  Takuji Oyama ,  Izumi Nakagome ,  Mayumi Satoh ,  Yoshino Nishio ,  Hiromi Nobusada ,  Shuichi Hirono ,  Kosuke Morikawa ,  Yuichi Hashimoto ,  Hiroyuki Miyachi
Affiliations
  • 1. Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
PMID: 21128600 DOI: 10.1021/jm101233f
Abstract

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.