Application of the phosphoramidate protide approach to the antiviral drug ribavirin

Ribavirin is a nucleoside analogue with antiviral activity against a number of DNA and RNA viruses in vitro and in vivo (Sidwell et al., 1972). Ribavirin has been approved for the treatment of respiratory syncytial virus and for the treatment of hepatitis C virus in association with interferon. The bioactivation of ribavirin involves intracellular phosphorylation to its 5′-monophosphate mediated by adenosine kinase followed by further phosphorylation to the di- and tri-phosphate. Its broad spectrum of antiviral activity prompted us to design and synthesise a new series of ribavirin phosphoramidates in order to investigate its activity against different viruses. The synthesis and the biological evaluation for these compounds will be reported