5-Fluorocytosine derivatives as inhibitors of deoxycytidine kinase

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6780-3. doi: 10.1016/j.bmcl.2009.09.082.
James E Tarver  1 ,  Theodore C Jessop ,  Marianne Carlsen ,  David J Augeri ,  Qinghong Fu ,  Jason P Healy ,  Alexander Heim-Riether ,  Amy Xu ,  Jerry A Taylor ,  Min Shen ,  Philip E Keyes ,  S David Kimball ,  Xuan-Chuan Yu ,  Maricar Miranda ,  Qingyun Liu ,  Jonathan C Swaffield ,  Amr Nouraldeen ,  Alan G E Wilson ,  Rick Finch ,  Kanchan Jhaver ,  Ann Marie Digeorge Foushee ,  Steve Anderson ,  Tamas Oravecz ,  Kenneth G Carson
Affiliations
  • 1. Lexicon Pharmaceuticals, Princeton, NJ 08540, United States.
PMID: 19836229 DOI: 10.1016/j.bmcl.2009.09.082
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.