Imidazopyridazine hepatitis C virus polymerase inhibitors. Structure-activity relationship studies and the discovery of a novel, traceless prodrug mechanism.
J Med Chem
; 57(5): 1964-75, 2014 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-24224729
ABSTRACT
By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodrug mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Piridazinas
/
Proteínas não Estruturais Virais
/
Hepacivirus
/
Inibidores Enzimáticos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article