| Autor: |
Manley PW; Oncology Research, Novartis Pharma AG, Basel, Switzerland. paul.manley@pharma.novartis.com, Furet P, Bold G, Brüggen J, Mestan J, Meyer T, Schnell CR, Wood J, Haberey M, Huth A, Krüger M, Menrad A, Ottow E, Seidelmann D, Siemeister G, Thierauch KH |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2002 Dec 19; Vol. 45 (26), pp. 5687-93. |
| DOI: |
10.1021/jm020899q |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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