Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors.
J Med Chem
; 45(26): 5687-93, 2002 Dec 19.
Article
em En
| MEDLINE
| ID: mdl-12477352
Two readily synthesized anthranilamide, VEGF receptor tyrosine kinase inhibitors have been prepared and evaluated as angiogenesis inhibitors. 2-[(4-Pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide (5) and N-3-isoquinolinyl-2-[(4-pyridinylmethyl)amino]benzamide (7) potently and selectively inhibit recombinant VEGFR-2 and VEGFR-3 kinases. As a consequence of their physicochemical properties, these anthranilamides readily penetrate cells and are absorbed following once daily oral administration to mice. Both 5 and 7 potently inhibit VEGF-induced angiogenesis in an implant model, with ED(50) values of 7 mg/kg. In a mouse orthotopic model of melanoma, 5 and 7 potently inhibited both the growth of the primary tumor as well as the formation of spontaneous peripheral metastases. The anthranilamides 5 and 7 represent a new structural class of VEGFR kinase inhibitors, which possess potent antiangiogenic and antitumor properties.
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Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Receptores de Fatores de Crescimento do Endotélio Vascular
/
Inibidores Enzimáticos
/
Ortoaminobenzoatos
/
Isoquinolinas
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Antineoplásicos
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article