Design, synthesis and biological evaluation of 4-piperazinyl-containing Chidamide derivatives as HDACs inhibitors

Bioorg Med Chem Lett. 2017 Jul 15;27(14):3162-3166. doi: 10.1016/j.bmcl.2017.05.026.

Qingwei Zhang ¹, Bingliu Lu ¹, Jianqi Li ²

Affiliations

1 Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Shanghai 201203, China; Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai 201203, China.
2 Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Shanghai 201203, China; Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai 201203, China. Electronic address: sipiqingwei@163.com.

PMID: 28532668 DOI: 10.1016/j.bmcl.2017.05.026

Abstract

The synthesis and biological evaluation of a variety of 4-piperazinyl-containing Chidamide derivatives is described. Some of these compounds were shown to inhibit HDAC1 with IC₅₀ values below micromolar range, and inhibited proliferation of several human Cancer cells, not possessing toxicity to human normal cells and hERG K⁺ ion channels. Compound 9g, proved to be the most potent and efficacious derivative in this series, was orally active in an HCT116 xenograft model in vivo.

Keywords

Anticancer activity; Chidamide derivatives; HDACs inhibitors; Molecular docking.

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