5-Fluorocytosine derivatives as inhibitors of deoxycytidine kinase
James E Tarver1, Theodore C Jessop, Marianne Carlsen
1Lexicon Pharmaceuticals, Princeton, NJ 08540, United States.
Bioorganic & Medicinal Chemistry Letters
|October 20, 2009
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.
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