Abstract
We have investigated the SAR of a series of pyrimidinone-containing Cdc7 kinase inhibitors. A wide range of amine substitutions give potent compounds with activities (K(i)) less than 1nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Amines / chemistry
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Amines / pharmacology
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Humans
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Minichromosome Maintenance Complex Component 2
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Nuclear Proteins / metabolism
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Phosphorylation / drug effects
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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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Protein Serine-Threonine Kinases / metabolism
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Pyrimidinones / chemistry*
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Pyrimidinones / pharmacology*
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Structure-Activity Relationship
Substances
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Amines
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Cell Cycle Proteins
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Nuclear Proteins
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Protein Kinase Inhibitors
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Pyrimidinones
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CDC7 protein, human
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Protein Serine-Threonine Kinases
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MCM2 protein, human
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Minichromosome Maintenance Complex Component 2