Evaluation of novel phosphoramidate ProTides of the 2'-fluoro derivatives of a potent anti-varicella zoster virus bicyclic nucleoside analogue.
Antivir Chem Chemother
; 21(1): 15-31, 2010 Oct 28.
Article
em En
| MEDLINE
| ID: mdl-21045257
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Ácidos Fosfóricos
/
Nucleosídeos de Pirimidina
/
Herpesvirus Humano 3
/
Flúor
/
Amidas
Idioma:
En
Revista:
Antivir Chem Chemother
Assunto da revista:
QUIMICA
/
TERAPIA POR MEDICAMENTOS
/
VIROLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido