Abstract
We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / classification
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Antineoplastic Agents / pharmacology*
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Aurora Kinases
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Crystallography, X-Ray
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Cyclin A / antagonists & inhibitors
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Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
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Drug Screening Assays, Antitumor
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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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Humans
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Models, Molecular
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Molecular Structure
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Pyrazoles / chemical synthesis
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Pyrazoles / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Cyclin A
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Enzyme Inhibitors
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Pyrazoles
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Aurora Kinases
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Protein Serine-Threonine Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2