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Eur J Med Chem. 2014 Oct 30;86:639-52. doi: 10.1016/j.ejmech.2014.09.024. Epub 2014 Sep 8.

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

Author information

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: tu_zhengchao@gibh.ac.cn.
5
Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: jiang_sheng@gibh.ac.cn.

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

PMID:
25218912
DOI:
10.1016/j.ejmech.2014.09.024
[Indexed for MEDLINE]

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