Abstract
Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).
Keywords:
2,4-Disubstituted pyrimidine; Cyclin dependent kinase inhibitor; Multiple myeloma; Polo-like kinase.
Copyright © 2018 Elsevier Ltd. All rights reserved.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Line, Tumor
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Cyclin-Dependent Kinase 9 / antagonists & inhibitors*
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Humans
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Molecular Structure
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Multiple Myeloma / drug therapy*
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Polo-Like Kinase 1
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Proto-Oncogene Proteins / antagonists & inhibitors
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Pyrimidines
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Protein Serine-Threonine Kinases
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CDK9 protein, human
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Cyclin-Dependent Kinase 9