Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease.
Bioorg Med Chem Lett
; 22(2): 1095-8, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-22189140
ABSTRACT
A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the protease-bound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring attached to the P2-proline 5-position. Isothermal calorimetric characterization of the role of hydrocarbon substitution of this six-membered ring, upon binding the HCV NS3 protease, was found to be exclusively entropic in nature. The synthesis, preliminary SAR and pharmacokinetic profiling of this compact, indolizidinone-derived scaffold are described.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas não Estruturais Virais
/
Inibidores Enzimáticos
/
Indolizinas
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2012
Tipo de documento:
Article