Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists

Shintaro Ban, Jun Ichi Kasuga, Izumi Nakagome, Hiromi Nobusada, Fusako Takayama, Shuichi Hirono, Hiromu Kawasaki, Yuichi Hashimoto, Hiroyuki Miyachi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

A series of α-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) α-selective agonists, based on our PPARα/δ dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPARα agonistic activity and PPARα selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model.

Original languageEnglish
Pages (from-to)3183-3191
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number10
DOIs
Publication statusPublished - May 15 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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