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

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. (C) 2015 Elsevier Masson SAS. All rights reserved.