Synthesis and evaluation of a new phosphorylated ribavirin prodrug

摘要: Ribavirin is an important broad-spectrum antiviral drug. However, its utilization can be limited by potential to cause hemolytic anemia as well variability in dosing levels and efficacy outcomes. To overcome these issues, we report on a new alkoxyalkylphosphodiester prodrug of ribavirin (2) that designed release the active ribavirin-monophosphate species selectively nucleated cells while limiting exposure anucleated red blood (RBCs). Prodrug 2 displays improved vitro activity against hepatitis C virus replicon influenza virus. Unlike ribavirin, does not significantly decrease ATP RBCs. demonstrates decreased uptake RBCs but increased HepG2 hepatocytes when compared ribavirin. In vivo, orally bioavailable well-tolerated rats which it processed accumulates liver. These results indicate has for safer, lower, less frequent, variable administration than