RESUMEN
We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Pirrolidinas/síntesis química , Triazinas/síntesis química , Familia-src Quinasas/antagonistas & inhibidores , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Inhibidores Enzimáticos del Citocromo P-450 , Perros , Inhibidores Enzimáticos/farmacocinética , Semivida , Humanos , Isoenzimas/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Ratones Desnudos , Modelos Moleculares , Conformación Molecular , Trasplante de Neoplasias , Unión Proteica , Pirrolidinas/farmacología , Ratas , Relación Estructura-Actividad , Triazinas/farmacologíaRESUMEN
A direct comparison of the inhibitory effects of alpha, beta, and gamma interferons (IFNs) on replication of a hepatitis C virus subgenomic replicon in a hepatoma cell line revealed similarities in antiviral potency. However, alternate IFN-induced antiviral mechanisms were suggested following observations of striking differences between IFN-gamma and IFN-alpha/beta with respect to strength and durability of the antiviral response and the magnitude and pattern of IFN-mediated gene expression.