Abstract
A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.
MeSH terms
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / chemical synthesis
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Deoxycytidine / chemistry
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Deoxycytidine / pharmacology
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Deoxycytidine Kinase / antagonists & inhibitors*
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Dose-Response Relationship, Drug
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Drug Design*
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Models, Molecular
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Molecular Structure
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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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Stereoisomerism
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Deoxycytidine
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Deoxycytidine Kinase
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5-fluoro-2'-deoxycytidine