Structure–activity relationship (SAR) studies of quinoxalines as novel HCV NS5B RNA-dependent RNA polymerase inhibitors

From chemical compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a substituted quinoxaline hit with an IC50 of 5.5 μM. A series of substituted quinoxaline amide derivatives were synthesized based on the hit’s pharmacophore, and a good structure–activity relationship was observed. Computer modeling analysis was employed to help comprehend the SAR.