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

Research output: Contribution to journalArticle

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)582-586
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number5
Publication statusPublished - 2014 May 8



  • C-H coupling
  • HDAC6
  • Histone deacetylase
  • inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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