Abstract
The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion and suitable to be scaled-up in view of possible lead development. Following a medicinal chemistry program aimed at improving cell permeability and selectivity, a series of compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit tumor cell proliferation has been obtained.
MeSH terms
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CDC2-CDC28 Kinases / antagonists & inhibitors*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Crystallization
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Crystallography, X-Ray
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Cyclin A / antagonists & inhibitors
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Cyclin-Dependent Kinase 2
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / classification*
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Enzyme Inhibitors / pharmacology*
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Humans
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Models, Molecular
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Molecular Structure
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Pyrazoles / chemical synthesis
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Pyrazoles / classification*
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Pyrazoles / pharmacology*
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Structure-Activity Relationship
Substances
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Cyclin A
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Enzyme Inhibitors
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Pyrazoles
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Glycogen Synthase Kinase 3