Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides.
Bioorg Med Chem
; 20(23): 6885-93, 2012 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-23085031
ABSTRACT
A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of α- and ß-anomers. The 6-chloropurine analogue was obtained as a mixture of N(7) and N(9) regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC(50)=36.9µM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
HIV-1
/
Hepacivirus
/
Nucleosídeos
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article