The application of the phosphoramidate ProTide approach confers micromolar potency against Hepatitis C virus on inactive agent 4′-azidoinosine: Kinase bypass on a dual base/sugar modified nucleoside

Novel phosphoramidate ProTides derived from 4'-azidoinosine have been prepared and evaluated in the replicon assay against hepatitis C Virus (HCV). The parent nucleoside analogue is inactive in this assay, while the ProTides are active at low mu M levels in some cases. This is a rare example of an inosine nucleoside analogue with potent antiviral activity and further supports the notion of ProTides as a drug discovery motif. (C) 2009 Elsevier Ltd. All rights reserved.