Abstract
A series of 4-(4-hydroxyphenyl)-6-phenylpyrimidin-2(1H)-ones were identified by HTS as inhibitors of CDC7. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus on removing potential metabolic liabilities and improving cellular potency.
MeSH terms
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Binding Sites
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Caco-2 Cells
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / chemistry*
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Indazoles / chemistry
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Inhibitory Concentration 50
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Models, Chemical
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Molecular Conformation
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Molecular Structure
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemistry*
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Pyrimidinones / chemistry
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Structure-Activity Relationship
Substances
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Cell Cycle Proteins
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Enzyme Inhibitors
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Indazoles
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Pyrimidinones
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CDC7 protein, human
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Protein Serine-Threonine Kinases