Anchimerically Activatable Antiviral ProTides.
ACS Med Chem Lett
; 8(9): 958-962, 2017 Sep 14.
Article
en En
| MEDLINE
| ID: mdl-28947944
ABSTRACT
This work describes the synthesis and biological evaluation of an anchimerically activated proTide of 2'-C-ß-methylguanosine as an inhibitor of dengue virus 2 (DENV-2). The proTide incorporates a chemically cleavable 2-(methylthio)ethyl moiety and a HINT1 hydrolyzable tryptamine phosphoramidate. Inhibition of DENV-2 replication by proTide 6 was 5-fold greater than the parent nucleoside while displaying no apparent cytotoxicity. Furthermore, we demonstrate with a HINT1 inhibitor that the anti DENV-2 activity of the proTide correlates with the activity of HINT1. Taken together, these results demonstrate that a phosphoramidate based pronucleotide that undergoes an initial nonenzymatic activation step based on anchimeric assistance followed by P-N bond cleavage by HINT1 can be prepared.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos