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

Abstract

AbstractHerein 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.