Discovery of a 2'-fluoro-2'-C-methyl C-nucleotide HCV polymerase inhibitor and a phosphoramidate prodrug with favorable properties.
Bioorg Med Chem Lett
; 27(8): 1840-1847, 2017 04 15.
Article
em En
| MEDLINE
| ID: mdl-28274633
ABSTRACT
A series of 2'-fluorinated C-nucleosides were prepared and tested for anti-HCV activity. Among them, the triphosphate of 2'-fluoro-2'-C-methyl adenosine C-nucleoside (15) was a potent and selective inhibitor of the NS5B polymerase and maintained activity against the S282T resistance mutant. A number of phosphoramidate prodrugs were then prepared and evaluated leading to the identification of the 1-aminocyclobutane-1-carboxylic acid isopropyl ester variant (53) with favorable pharmacokinetic properties including efficient liver delivery in animals.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Proteínas não Estruturais Virais
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Hepacivirus
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Nucleosídeos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2017
Tipo de documento:
Article