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

17 Citations (Scopus)

Abstract

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
Volume5
Issue number5
DOIs
Publication statusPublished - 2014 May 8
Externally publishedYes

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Histone Deacetylase Inhibitors
Derivatives
Molecules
Testing
2-aminothiazole

Keywords

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

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Late-stage C-H coupling enables rapid identification of HDAC inhibitors : Synthesis and evaluation of NCH-31 analogues. / Sekizawa, Hiromi; Amaike, Kazuma; Itoh, Yukihiro; Suzuki, Takayoshi; Itami, Kenichiro; Yamaguchi, Junichiro.

In: ACS Medicinal Chemistry Letters, Vol. 5, No. 5, 08.05.2014, p. 582-586.

Research output: Contribution to journalArticle

Sekizawa, Hiromi ; Amaike, Kazuma ; Itoh, Yukihiro ; Suzuki, Takayoshi ; Itami, Kenichiro ; Yamaguchi, Junichiro. / Late-stage C-H coupling enables rapid identification of HDAC inhibitors : Synthesis and evaluation of NCH-31 analogues. In: ACS Medicinal Chemistry Letters. 2014 ; Vol. 5, No. 5. pp. 582-586.
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