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 ORCID: https://orcid.org/0000-0002-9728-3419, Andrei, Graciela, Snoeck, Robert, Balzarini, Jan and McGuigan, Christopher ORCID: https://orcid.org/0000-0001-8409-710X 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. 10.3851/IMP1661

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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
Date Type:	Publication
Status:	Published
Schools:	Schools > Pharmacy Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RS Pharmacy and materia medica
Publisher:	International Medical Press
ISSN:	0956-3202
Last Modified:	05 Jan 2024 05:57
URI:	https://orca.cardiff.ac.uk/id/eprint/7430

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