Synthesis and biological evaluation of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as adenosine kinase inhibitors.
The synthesis and structure-activity relationship of a series of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as novel non-nucleoside adenosine kinase inhibitors is described. A variety of substituents, primarily aryl, at the C6 and C7 positions of the pyridopyrimidine core were found to yield analogues that are potent inhibitors of adenosine kinase. In contrast to the 5,7-disubstituted and 5,6,7-trisubstituted pyridopyrimidine series, these analogues exhibited only modest potency to inhibit AK in intact cells.
Perner
Richard J
RJ
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6115, USA. richard.j.perner@abbott.com
Lee
Chih-Hung
CH
Jiang
Meiqun
M
Gu
Yu-Gui
YG
Didomenico
Stanley
S
Bayburt
Erol K
EK
Alexander
Karen M
KM
Kohlhaas
Kathy L
KL
Jarvis
Michael F
MF
Kowaluk
Elizabeth L
EL
Bhagwat
Shripad S
SS
D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D000248:Adenosine Kinase