Discovery of N-(4'-(indol-2-yl)phenyl)sulfonamides as novel inhibitors of HCV replication.
Bioorg Med Chem Lett
; 23(13): 3942-6, 2013 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-23683596
ABSTRACT
A series of novel 2-phenylindole analogs were synthesized and evaluated for activity in subgenomic HCV replicon inhibition assays. Several compounds containing small alkyl sulfonamides on the phenyl ring exhibiting submicromolar EC50 values against the genotype 1b replicon were identified. Among these, compound 25d potently inhibited the 1b replicon (EC50=0.17 µM) with 147-fold selectivity with respect to cytotoxicity. Compound 25d was stable in the presence of human liver microsomes and had a good pharmacokinetic profile in rats with an IV half-life of 4.3h and oral bioavailability (F) of 58%.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Sulfonamidas
/
Replicação Viral
/
Microssomos Hepáticos
/
Hepacivirus
/
Descoberta de Drogas
/
Indóis
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos