Structure-activity relationship (SAR) studies of quinoxalines as novel HCVNS5B 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 mu M. 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. (c) 2007 Elsevier Ltd. All rights reserved.