Synthesis of 9-(2-β-C-methyl-β-d-ribofuranosyl)-6-substituted purine derivatives as inhibitors of HCV RNA replication

A series of 9-(2′-β-C-methyl-β-d-ribofuranosyl)-6-substituted purine derivatives were synthesized as potential inhibitors of HCV RNA replication. Their inhibitory activities in a cell based HCV replicon assay were reported. A prodrug approach was used to further improve the potency of these compounds by increasing the intracellular levels of 5′-monophosphate metabolites. These nucleotide prodrugs showed much improved inhibitory activities of HCV RNA replication.