A Cyclic Phosphoramidate Prodrug of 2′-Deoxy-2′-Fluoro-2′- C -Methylguanosine for the Treatment of Dengue Virus Infection

Abstract

Monophosphate prodrug analogs of 2′-deoxy-2′-fluoro-2′- C -methylguanosine have been reported as potent inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase. These prodrugs also display potent anti-dengue virus activities in cellular assays although their prodrug moieties were designed to produce high levels of triphosphate in the liver. Since peripheral blood mononuclear cells (PBMCs) are among the major targets of dengue virus, different prodrug moieties were designed to effectively deliver 2′-deoxy-2′-fluoro-2′- C -methylguanosine monophosphate prodrugs and their corresponding triphosphates into PBMCs after oral administration.