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

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.