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: [email protected].
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.