RESUMO
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.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Pirrolidinas/síntese química , Triazinas/síntese química , Quinases da Família src/antagonistas & inibidores , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Inibidores das Enzimas do Citocromo P-450 , Cães , Inibidores Enzimáticos/farmacocinética , Meia-Vida , Humanos , Isoenzimas/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Nus , Modelos Moleculares , Conformação Molecular , Transplante de Neoplasias , Ligação Proteica , Pirrolidinas/farmacologia , Ratos , Relação Estrutura-Atividade , Triazinas/farmacologiaRESUMO
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.