I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles

SAR development of palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead I is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. Further SAR development resulted in novel NS5B polymerase inhibitors exemplified by 7r with improved enzyme and replicon activity.