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

  • Eur J Med Chem. 2014 Oct 30:86:639-52. doi: 10.1016/j.ejmech.2014.09.024.
Yiwu Yao  1 ,  Chenzhong Liao  2 ,  Zheng Li  3 ,  Zhen Wang  1 ,  Qiao Sun  1 ,  Chunping Liu  1 ,  Yang Yang  2 ,  Zhengchao Tu  4 ,  Sheng Jiang  5
Affiliations
  • 1. Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • 2. School of Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.
  • 3. The Methodist Hospital Research Institute, Houston, TX 77030, USA.
  • 4. Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: [email protected].
  • 5. Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: [email protected].
PMID: 25218912 DOI: 10.1016/j.ejmech.2014.09.024
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.

Keywords
HDAC; Isoforms selectivity; Scaffold-hopping; Structure–activity relationship.