ABSTRACT The present study attempts to investigate the 4,6-diphenylpyrimidine substituted benzamide derivatives that act as HDAC inhibitors. Histone deacetylases (HDACs) have been widely recognized as promising targets for cancer treatment. It has been three decades ago, that the first potent Zn2+ dependent histone deacetylase inhibitor was recognized. Meanwhile, to date, SAHA (Vorinostat), Belinostat (PXD-101), Panobinostat (LBH-589), and Romidepsin (FK-228) four HDAC inhibitors have been approved by FDA for cancer chemotherapy, while more than 10 HDAC inhibitors have entered in clinical trials for the development of therapeutic agents for oncological as well as other medical indications. Beyond this, the clinical utility of HDAC inhibitors is a major obstacle to intrinsic drug resistance and various side effects including thrombocytopenia, neutropenia, nausea, fatigue, and vomiting. So, discovering a novel potential scaffold is still in great demand. Distinctive features of HDAC inhibitors include a Zn2+ binding moiety, a carbon linker, and a capping group. To better understand the structural requirements of HDAC inhibitors, a small molecule with cap group as substituted 4,6-diphenylpyrimidine of functional groups adjacent to the metal-binding benzamide was designed in our study to improve pharmacokinetic parameters and to reduce adverse effects through in silico studies. Keywords: HDAC enzyme, HDAC inhibitor, Benzamide, 4, 6-diphenylpyrimidine.