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.
Evaluation of novel phosphoramidate ProTides of the 2′-fluoro derivatives of a potent anti-varicella zoster virus bicyclic nucleoside analogue
[Category] 두창, 수두, 홍역,
Pubmed URL [DOI] 10.3851/IMP1661
[Source] pubmed
All Keywords