Use of 2'-spirocyclic ethers in HCV nucleoside design.
J Med Chem
; 57(5): 1826-35, 2014 Mar 13.
Article
en En
| MEDLINE
| ID: mdl-24079820
ABSTRACT
Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS5B polymerase, with IC50 = 8.48 µM. Activity against NS5B bearing the S282T mutation was reduced. Phosphoramidate prodrugs of a 2'-oxetane 2-amino-6-O-methyl-purine nucleoside demonstrated potent anti-HCV activity in vitro, and the corresponding triphosphate retained similar potent activity against both wild-type and S282T HCV NS5B polymerase.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Diseño de Fármacos
/
Hepacivirus
/
Citidina
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos