Development of 2-thioxoquinazoline-4-one derivatives as dual and selective inhibitors of dynamin-related protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA)

Akiyoshi Numadate, Yusuke Mita, Yotaro Matsumoto, Shinya Fujii, Yuichi Hashimoto

研究成果: Article査読

9 被引用数 (Scopus)

抄録

An established inhibitor ot dynamin-related protein 1 (Drp1), 3-(2,4-dichloro-5-methoxyphenyl)- 2- thioxoquinazoline-4-one (mdivi-1), was recently reported also to show potent puromycin-sensitive aminopeptidase (PSA)-inhibitory activity. Herein, we report structural development of mdivi-1 derivatives and structure-activity relationship (SAR) analysis of the synthesized compounds, as well as the structurally related PSA-specific inhibitor 3-(2,6-diethylphenyl)quinazoline-2,4-dione (PAQ-22), with the aim of identifying key structural features for inhibitory activity in order to develop selective inhibitors of Drpl, which is a potential target for treatment of Huntington's disease. Among the synthesized compounds, 3-(4-chloro3methoxyphenyl)-2-thioxoquinazoline-4-one 10g) exhibited more potent Drpl-inhibitory activity than mdivi-1 with high selectivity for Drpl over PSA.

本文言語English
ページ(範囲)979-988
ページ数10
ジャーナルChemical and Pharmaceutical Bulletin
62
10
DOI
出版ステータスPublished - 2014 10 1
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 創薬

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