Late-stage C-H coupling enables rapid identification of HDAC inhibitors: Synthesis and evaluation of NCH-31 analogues

Hiromi Sekizawa, Kazuma Amaike, Yukihiro Itoh, Takayoshi Suzuki, Kenichiro Itami, Junichiro Yamaguchi

研究成果: Article査読

23 被引用数 (Scopus)

抄録

We previously reported the discovery of NCH-31, a potent histone deacetylase (HDAC) inhibitor. By utilizing our C-H coupling reaction, we rapidly synthesized 16 analogues (IYS-1 through IYS-15 and IYS-Me) of NCH-31 with different aryl groups at the C4-position of 2-aminothiazole core of NCH-31. Subsequent biological testing of these derivatives revealed that 3-fluorophenyl (IYS-10) and 4-fluorophenyl (IYS-15) derivatives act as potent pan-HDAC inhibitor. Additionally, 4-methylphenyl (IYS-1) and 3-fluoro-4-methylphenyl (IYS-14) derivatives acted as HDAC6-insensitive inhibitors. The present work clearly shows the power of the late-stage C-H coupling approach to rapidly identify novel and highly active/selective biofunctional molecules.

本文言語English
ページ(範囲)582-586
ページ数5
ジャーナルACS Medicinal Chemistry Letters
5
5
DOI
出版ステータスPublished - 2014 5 8
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 創薬
  • 有機化学

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