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 journalArticle

15 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

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Peroxisome Proliferator-Activated Receptors
Acids
Lead compounds
Molecular modeling
Structure-Activity Relationship
Animals
Animal Models
Derivatives
Non-alcoholic Fatty Liver Disease

ASJC Scopus subject areas

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

Cite this

Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists. / Ban, Shintaro; Kasuga, Jun Ichi; Nakagome, Izumi; Nobusada, Hiromi; Takayama, Fusako; Hirono, Shuichi; Kawasaki, Hiromu; Hashimoto, Yuichi; Miyachi, Hiroyuki.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 10, 15.05.2011, p. 3183-3191.

Research output: Contribution to journalArticle

Ban, Shintaro ; Kasuga, Jun Ichi ; Nakagome, Izumi ; Nobusada, Hiromi ; Takayama, Fusako ; Hirono, Shuichi ; Kawasaki, Hiromu ; Hashimoto, Yuichi ; Miyachi, Hiroyuki. / Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 10. pp. 3183-3191.
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