To explore novel histone deacetylase (HDACs) inhibitors with anti-tumor activity, MS-275, a HDACs inhibitor, was prepared and used as a lead compound to design new N-substituted benzamide derivatives.  MS-275 and eleven target compounds were obtained, and their structures were confirmed by ¹H NMR and HR-MS individually.  The results showed that the activity of compound 9d was equal to MS-275 in HDACs  inhibition tests in vitro and worthy of further investigation.  Compound 5c, 5d and 9c displayed obvious dose-effect relationship, which possessed moderate HDACs inhibitory activities.  Ten compounds except 9e  had selective inhibitory activities on Hut78.