1. Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States;2. Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States
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.