Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression

Yosuke Toyota, Sayaka Nomura, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC50: 14 μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone.

本文言語English
ページ(範囲)2776-2780
ページ数5
ジャーナルBioorganic and Medicinal Chemistry Letters
27
12
DOI
出版ステータスPublished - 2017
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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