Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class i and IIb histone deacetylase inhibitors

Yiwu Yao, Chenzhong Liao, Zheng Li, Zhen Wang, Qiao Sun, Chunping Liu, Yang Yang, Zhengchao Tu, Sheng Jiang

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

A novel series of HDAC inhibitors demonstrating class I and IIb subtype selectivity have been identified using a scaffold-hopping strategy. Several designed compounds showed better selectivity for class I and IIb over class IIa HDAC isoforms comparing to the FDA approved HDAC targeting drug SAHA. A representative lead compound 22 bearing a biphenyl moiety demonstrated promising class I and IIb HDAC isoforms selectivity and in vitro anticancer activities against several cancer cell lines. This work could serve as a fundamental platform for further exploration of selective HDAC inhibitors using designed molecular scaffold.

Original languageEnglish (US)
Pages (from-to)639-652
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume86
DOIs
StatePublished - Oct 30 2014

Keywords

  • HDAC
  • Isoforms selectivity
  • Scaffold-hopping
  • Structureeactivity relationship

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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