Synthesis and biological evaluation of 2,4-diaminopyrimidine-5-carbonitrile and N-(2-amino-5-cyanopyrimidin-4-yl)benzamide derivatives as EGFR inhibitors

A series of 2,4-diaminopyrimidine-5-carbonitrile and N-(2-amino-5-cyanopyrimidin-4-yl) benzamide derivatives (5–14) were synthesized and their chemical structures were confirmed by 1 H, 13C NMR and mass spectral data. Anticancer activity of all the synthesized compounds were evaluated for in vitro cytotoxic activity against a panel of four human cancer cell lines i.e., human breast (MCF-7,), cervical cancer (C33A), oral (KB) and prostrate (DU-145). All the examined compounds, demonstrated potent to moderate anticancer activity. Among all the synthesized compounds, 6 and 11 were exhibited more potent activity. Docking studies for 6 and 11 into EGFR active site was carried out to investigate their potential binding modes. Therefore, compounds 6 and 11 can be considered as fascinating candidates for further expansion of more potent anticancer agents.