1.
Bioorg Med Chem Lett
; 18(3): 959-62, 2008 Feb 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-18182285
RESUMO
Novel 4-anilino-1H-pyrazolo[3,4-d]pyrimidines have been synthesized and evaluated in vitro for erbB2 and EGFR kinase inhibition. A representative compound displaying oral bioavailability in rat and dog illustrates the potential of this series to provide orally active erbB2 inhibitors.
Assuntos
Inibidores de Proteínas Quinases/antagonistas & inibidores , Pirazóis/síntese química , Pirazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptor ErbB-2/antagonistas & inibidores , Animais , Técnicas de Química Combinatória , Cães , Desenho de Fármacos , Estrutura Molecular , Pirazóis/administração & dosagem , Pirazóis/química , Pirimidinas/administração & dosagem , Pirimidinas/química , Ratos
2.
Bioorg Med Chem Lett
; 17(22): 6326-9, 2007 Nov 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17869514
RESUMO
Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase.