5-Fluorocytosine derivatives as inhibitors of deoxycytidine kinase.
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.
Tarver
James E
JE
Lexicon Pharmaceuticals, Princeton, NJ 08540, United States.
Jessop
Theodore C
TC
Carlsen
Marianne
M
Augeri
David J
DJ
Fu
Qinghong
Q
Healy
Jason P
JP
Heim-Riether
Alexander
A
Xu
Amy
A
Taylor
Jerry A
JA
Shen
Min
M
Keyes
Philip E
PE
David Kimball
S
S
Yu
Xuan-Chuan
XC
Miranda
Maricar
M
Liu
Qingyun
Q
Swaffield
Jonathan C
JC
Nouraldeen
Amr
A
Wilson
Alan G E
AG
Finch
Rick
R
Jhaver
Kanchan
K
Foushee
Ann Marie Digeorge
AM
Anderson
Steve
S
Oravecz
Tamas
T
Carson
Kenneth G
KG
D000818:Animals; D003842:Deoxycytidine Kinase / Q000037:antagonists & inhibitors*; D015195:Drug Design; D005437:Flucytosine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D005437:Flucytosine; D003842:Deoxycytidine Kinase