Abstract
A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Female
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Isoquinolines / chemical synthesis
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Isoquinolines / pharmacokinetics
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Mice
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Mice, Inbred Strains
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Phthalazines / administration & dosage
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Phthalazines / chemical synthesis
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Phthalazines / pharmacokinetics*
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Piperidines
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Quinazolines
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Substances
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IM-094482 57
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Isoquinolines
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Phthalazines
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Piperidines
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Quinazolines
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2
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vandetanib