Title: Evaluation of novel phosphoramidate ProTides of the 2'-fluoro derivatives of a potent anti-varicella zoster virus bicyclic nucleoside analogue
Authors: Derudas, Marco ×
Quintiliani, Maurizio
Brancale, Andrea
Andrei, Graciela
Snoeck, Robert
Balzarini, Jan
McGuigan, Christopher #
Issue Date: Oct-2010
Publisher: Blackwell Scientific Publications
Series Title: Antiviral Chemistry & Chemotherapy vol:21 issue:1 pages:15-31
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.
ISSN: 0956-3202
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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