Discovery of Thienoimidazole-Based HCV NS5A Genotype 1a and 1b Inhibitors.
ACS Med Chem Lett
; 5(3): 240-3, 2014 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-24900811
ABSTRACT
The discovery of potent thienoimidazole-based HCV NS5A inhibitors is herein reported. A novel method to access the thienoimidazole [5,5]-bicyclic system is disclosed. This method gave access to a common key intermediate (6) that was engaged in Suzuki or Sonogashira reactions with coupling partners bearing different linkers. A detailed study of the structure-activity relationship (SAR) of the linkers revealed that aromatic linkers with linear topologies are required to achieve high potency for both 1a and 1b HCV genotypes. Compound 20, with a para-phenyl linker, was identified as a potential lead displaying potencies of 17 and 8 pM against genotype 1a and 1b replicons, respectively.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos