Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication

Abstract

In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45μM, respectively) and 6d (IC50/90=0.116/0.452μM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.