Design, synthesis and antiproliferative activities of novel benzamides derivatives as HDAC inhibitors

Eur J Med Chem. 2015 Jul 15:100:270-6. doi: 10.1016/j.ejmech.2015.05.045.

Yanyang Li ¹, Yongzhen Wang ¹, Ning Xie ², Ming Xu ², Pengyu Qian ², Yanjin Zhao ¹, Shuxin Li ³

Affiliations

1 Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
2 Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
3 Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China. Electronic address: lisx28@163.com.

PMID: 26140961 DOI: 10.1016/j.ejmech.2015.05.045

Abstract

Guided by the principle of nonclassical electronic isosterism and structural optimization, a series of novel HDAC inhibitors bearing a bicyclic heterocycle moiety were designed and synthesized based on the lead compound of MS-275. All the prepared compounds were evaluated for their in vitro antiproliferative activities against HCT-116, MCF-7 and A549 human Cancer cell lines, all compounds exerted excellent antitumor activities. Moreover, the compound 4a exhibited an acceptable pharmacokinetic profile with bio-availability in rat of 76% and could be considered as a candidate compound for further development.

Keywords

Acrylamide; Antiproliferative; Benzamides derivatives; HDAC; Pharmacokinetic; Synthesis.

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