Novel substituted pyrimidines as HCV replication (replicase) inhibitors.
Bioorg Med Chem Lett
; 22(2): 1160-4, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-22178556
ABSTRACT
Compound 1 was identified as a HCV replication inhibitor from screening/early SAR triage. Potency improvement was achieved via modulation of substituent on the 5-azo linkage. Due to potential toxicological concern, the 5-azo linkage was replaced with 5-alkenyl or 5-alkynyl moiety. Analogs containing the 5-alkynyl linkage were found to be potent inhibitors of HCV replication. Further evaluation identified compounds 53 and 63 with good overall profile, in terms of replicon potency, selectivity and in vivo characteristics. Initial target engagement studies suggest that these novel carbanucleoside-like derivatives may inhibit the HCV replication complex (replicase).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Replicação Viral
/
Hepatite C
/
Hepacivirus
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article