Abstract
A series of potent piperidine-linked cytosine derivatives were prepared as inhibitors of deoxycytidine kinase (dCK). Compound 9h was discovered to be a potent inhibitor of dCK and shows a good combination of cellular potency and pharmacokinetic parameters. Compound 9h blocks the incorporation of radiolabeled cytosine into mouse T-cells in vitro, as well as in vivo in mice following a T-cell challenge.
MeSH terms
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Animals
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Deoxycytidine Kinase / antagonists & inhibitors*
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Drug Design
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Flucytosine / chemical synthesis
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Flucytosine / chemistry
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Flucytosine / pharmacology*
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Humans
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Mice
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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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Flucytosine
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Deoxycytidine Kinase