Adenosine kinase inhibitors: polar 7-substitutent of pyridopyrimidine derivatives improving their locomotor selectivity.
We have discovered that polar 7-substituents of pyridopyrimidine derivatives affect not only whole cell AK inhibitory potency, but also selectivity in causing locomotor side effects in vivo animal models. We have identified compound, 1o, which has potent whole cell AK inhibitory potency, analgesic activity and minimal reduction of locomotor activity.
Zheng
Guo Zhu
GZ
Abbott Laboratories, Neuroscience Research, Bldg. AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. guozhu.zheng@abbott.com
Mao
Yue
Y
Lee
Chih-Hung
CH
Pratt
John K
JK
Koenig
John R
JR
Perner
Richard J
RJ
Cowart
Marlon D
MD
Gfesser
Gregory A
GA
McGaraughty
Steve
S
Chu
Katharine L
KL
Zhu
Chang
C
Yu
Haixia
H
Kohlhaas
Kathy
K
Alexander
Karen M
KM
Wismer
Carol T
CT
Mikusa
Joseph
J
Jarvis
Michael F
MF
Kowaluk
Elizabeth A
EA
Stewart
Andrew O
AO
D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D009043:Motor Activity / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000700:Analgesics; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D000248:Adenosine Kinase