Design, Synthesis, in Silico and Biological Evaluation of Novel 4‐Aminopyrimidine‐5‐carbonitriles

Abstract Herein we report that 4‐aminopyrimidine‐5‐carbonitriles 3 a – i were efficiently synthesized by reacting suitable 2‐(ethoxyalkylene)malononitriles 1 a – c with easily available amidine hydrochlorides 2 a – d , in good yields using a simple synthetic scheme. To predict their pharmacological properties a comprehensive in silico analysis was conducted. Consequently, appropriate compounds 3 a – h were screened for their antiproliferative activity against two colorectal‐cancer‐cell lines and one lung cancer cell line. These analyses revealed that 4‐amino‐6‐methyl‐2‐( p ‐tolyl) pyrimidine‐5‐carbonitrile ( 3 c ) and 4‐amino‐2‐(4‐chlorophenyl)‐6‐methyl pyrimidine‐5‐carbonitrile ( 3 h ) exhibited the most potent inhibitory activity against human LoVo and HCT‐116 cancer cells, and that the most potent inhibitory activity against human A549 cells was observed for compound 3 h .