Benzimidazole Inhibitors of Hepatitis C Virus NS5B Polymerase: Identification of 2-[(4-Diarylmethoxy)phenyl]-benzimidazole.

Abstract A series of 1-cycloalkyl-2-phenyl-1H-benzimidazole-5-carboxylic acid derivatives was synthesized and evaluated for inhibitory activity against HCV NS5B RNA-dependent RNA polymerase (RdRp). A SAR study was performed and led to identify the 2-[(4-diarylmethoxy)phenyl]-benzimidazoles as potent inhibitors. They inhibit subgenomic HCV RNA replication in the replicon cells at low micromolar concentrations (EC50 as low as 1.1 μM). They are selective against DNA polymerases (IC50 > 10 μM) and exhibit low cytotoxicity.