Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors.

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Manley PW, Furet P, Bold G, Bruggen J, Mestan J, Meyer T, Schnell CR, Wood J, Haberey M, Huth A, Kruger M, Menrad A, Ottow E, Seidelmann D, Siemeister G, Thierauch KH

Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors.

J Med Chem. 2002 Dec 19;45(26):5687-93.

PubMed ID

12477352 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Semaxanib	Vascular endothelial growth factor receptor 2	IC 50 (nM)	1300	N/A	N/A	Details
Semaxanib	Vascular endothelial growth factor receptor 2	IC 50 (nM)	220	N/A	N/A	Details
Semaxanib	Vascular endothelial growth factor receptor 2	IC 50 (nM)	884	N/A	N/A	Details