Pyrazolo[1,5- a]pyrimidine-based inhibitors of HCV polymerase

Synthesis and optimization of novel pyrazolo[1,5- a]pyrimidine HCV polymerase inhibitors are described. The present paper describes a novel series of HCV RNA polymerase inhibitors based on a pyrazolo[1,5- a]pyrimidine scaffold bearing hydrophobic groups and an acidic functionality. Several compounds were optimized to low nanomolar potencies in a biochemical RdRp assay. SAR trends clearly reveal a stringent preference for a cyclohexyl group as one of the hydrophobes, and improved activities for carboxylic acid derivatives.