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

Masao Ohashi, Takuji Oyama, Izumi Nakagome, Mayumi Satoh, Yoshino Nishio, Hiromi Nobusada, Shuichi Hirono, Kosuke Morikawa, Yuichi Hashimoto, Hiroyuki Miyachi

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)331-341
Number of pages11
JournalJournal of Medicinal Chemistry
Volume54
Issue number1
DOIs
Publication statusPublished - Jan 13 2011

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PPAR gamma
Ligands
Acids
Transcriptional Activation
Lipoproteins
Homeostasis
Transcription Factors
Lipids
Glucose
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Design, synthesis, and structural analysis of phenylpropanoic acid-type PPARγ-selective agonists : Discovery of reversed stereochemistry-activity relationship. / Ohashi, Masao; Oyama, Takuji; Nakagome, Izumi; Satoh, Mayumi; Nishio, Yoshino; Nobusada, Hiromi; Hirono, Shuichi; Morikawa, Kosuke; Hashimoto, Yuichi; Miyachi, Hiroyuki.

In: Journal of Medicinal Chemistry, Vol. 54, No. 1, 13.01.2011, p. 331-341.

Research output: Contribution to journalArticle

Ohashi, M, Oyama, T, Nakagome, I, Satoh, M, Nishio, Y, Nobusada, H, Hirono, S, Morikawa, K, Hashimoto, Y & Miyachi, H 2011, 'Design, synthesis, and structural analysis of phenylpropanoic acid-type PPARγ-selective agonists: Discovery of reversed stereochemistry-activity relationship', Journal of Medicinal Chemistry, vol. 54, no. 1, pp. 331-341. https://doi.org/10.1021/jm101233f
Ohashi, Masao ; Oyama, Takuji ; Nakagome, Izumi ; Satoh, Mayumi ; Nishio, Yoshino ; Nobusada, Hiromi ; Hirono, Shuichi ; Morikawa, Kosuke ; Hashimoto, Yuichi ; Miyachi, Hiroyuki. / Design, synthesis, and structural analysis of phenylpropanoic acid-type PPARγ-selective agonists : Discovery of reversed stereochemistry-activity relationship. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 1. pp. 331-341.
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