Abstract
A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3beta.
MeSH terms
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Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
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Drug Evaluation, Preclinical
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Drug Screening Assays, Antitumor
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Glycogen Synthase Kinase 3 beta
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Models, Molecular
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacology*
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Pyridazines / chemical synthesis*
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Pyridazines / pharmacology*
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Substances
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Protein Kinase Inhibitors
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Pyridazines
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Vascular Endothelial Growth Factor Receptor-2
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Glycogen Synthase Kinase 3 beta
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Cyclin-Dependent Kinase 4
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Glycogen Synthase Kinase 3