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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. 2009
Christopher McGuigan, and
Felice Daverio, and
Isabel Nájera, and
Joseph A Martin, and
Klaus Klumpp, and
David B Smith
Welsh School of Pharmacy, Cardiff University, Cardiff, UK. mcguigan@cardiff.ac.uk
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 microM 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.
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