Abstract
Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.
MeSH terms
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Administration, Oral
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Aminopyridines / chemical synthesis
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Aminopyridines / chemistry*
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Aminopyridines / pharmacokinetics
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Aminopyridines / pharmacology*
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Animals
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Biological Availability
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Edema / drug therapy
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Edema / metabolism
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Female
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Inhibitory Concentration 50
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Mice
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Models, Molecular
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacokinetics
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Pyrazoles / pharmacology
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Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors*
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Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
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Structure-Activity Relationship
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Urea / analogs & derivatives*
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Urea / chemical synthesis
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Urea / pharmacology
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Uterine Diseases / drug therapy
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Uterine Diseases / metabolism
Substances
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Aminopyridines
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Protein Kinase Inhibitors
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Pyrazoles
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Urea
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Receptors, Platelet-Derived Growth Factor
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Receptors, Vascular Endothelial Growth Factor