5,6,7-trisubstituted 4-aminopyrido[2,3-d]pyrimidines as novel inhibitors of adenosine kinase.
The synthesis and structure-activity relationship of a series of 5,6,7-trisubstituted 4-aminopyrido[2,3-d]pyrimidines as novel nonnucleoside adenosine kinase inhibitors is described. A variety of alkyl, aryl, and heteroaryl substituents were found to be tolerated at the C5, C6, and C7 positions of the pyridopyrimidine core. These studies have led to the identification of analogues that are potent inhibitors of adenosine kinase with in vivo analgesic activity.
Perner
Richard J
RJ
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6115, USA. richard.j.perner@abbott.com
Gu
Yu-Gui
YG
Lee
Chih-Hung
CH
Bayburt
Erol K
EK
McKie
Jeffery
J
Alexander
Karen M
KM
Kohlhaas
Kathy L
KL
Wismer
Carol T
CT
Mikusa
Joe
J
Jarvis
Michael F
MF
Kowaluk
Elizabeth A
EA
Bhagwat
Shripad S
SS
D000248:Adenosine Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D010147:Pain Measurement; D010766:Phosphorylation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000700:Analgesics; D011725:Pyridines; D011743:Pyrimidines; D000248:Adenosine Kinase