Abstract
A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.
MeSH terms
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Animals
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Disease Models, Animal
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Edema / chemically induced
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Estradiol
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Female
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Mice
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Models, Molecular
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Pyridines / chemical synthesis*
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Pyridines / pharmacology
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Structure-Activity Relationship
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Urea / chemical synthesis*
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Urea / chemistry
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Urea / pharmacology
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Uterine Diseases / pathology
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Substances
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Pyridines
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thienopyridine
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Estradiol
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Urea
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Vascular Endothelial Growth Factor Receptor-2