Evaluation of novel phosphoramidate ProTides of the 2′-fluoro derivatives of a potent anti-varicella zoster virus bicyclic nucleoside analogue

Derudas, Marco, Quintiliani, Maurizio, Brancale, Andrea, Andrei, Graciela, Snoeck, Robert, Balzarini, Jan and McGuigan, Christopher (2010) Evaluation of novel phosphoramidate ProTides of the 2′-fluoro derivatives of a potent anti-varicella zoster virus bicyclic nucleoside analogue. Antiviral Chemistry and Chemotherapy, 21 (1). pp. 15-31. ISSN 2040-2066

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Abstract

Background: Recently, the synthesis and antiviral activity of a series of 2′-fluoro derivatives of the most potent anti-varicella zoster virus (VZV) agent reported to date, the bicyclic nucleoside analogue Cf1743, have been reported.

Methods: Here, we present molecular modelling studies for the interaction of these compounds with VZV-encoded thymidine kinase (TK) and we report the synthesis of a series of phosphoramidate ProTides of these compounds designed to bypass the nucleoside kinase dependence of the parent nucleoside analogues.

Results: The phosphoramidate prodrugs were equally effective as their parent compounds against VZV in cell culture, but lost antiviral potency against TK-deficient VZV strains.

Conclusions: ProTide-based kinase bypass is not successful in this case.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: Marco Derudas
Date Deposited: 23 Jul 2015 06:16
Last Modified: 23 Jul 2015 06:16
URI: http://sro.sussex.ac.uk/id/eprint/55688
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