The Synthesis and Biological Evaluation of N-Substituted 1H-Benzimidazol-2-yl-1H-pyrazole-3,5-diamines

摘要

The synthesis of 1H-benzimidazol-2-yl-1H-pyrazole-3,5-diamines has been developed. Synthesized bisheteroaryls contain two privileged medicinal scaffolds, aminopyrazole and benzimidazole, with two diversity positions at N1 of benzimidazole and C3 of pyrazole, respectively. The three-step synthesis includes the Mitsunobu N-alkylation of benzimidazole and subsequent one-pot formation of aminopyrazole involving substitution of methylthio groups with amine and hydrazine followed with final ring closure. Inhibitory activity toward cyclin-dependent kinase 2/cyclin E and cytotoxicity against two cancer cell lines were evaluated for all novel pyrazoles. Two compounds showed modest cyclin-dependent kinase inhibition activity and cytotoxicity against cancer cell lines K562 and MCF7.