Pyridopyrimidine analogues as novel adenosine kinase inhibitors.
A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.
Zheng
G Z
GZ
Abbott Laboratories, Dept. 4PM, Bldg. AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. guozhu.zheng@abbott.com
Lee
C
C
Pratt
J K
JK
Perner
R J
RJ
Jiang
M Q
MQ
Gomtsyan
A
A
Matulenko
M A
MA
Mao
Y
Y
Koenig
J R
JR
Kim
K H
KH
Muchmore
S
S
Yu
H
H
Kohlhaas
K
K
Alexander
K M
KM
McGaraughty
S
S
Chu
K L
KL
Wismer
C T
CT
Mikusa
J
J
Jarvis
M F
MF
Marsh
K
K
Kowaluk
E A
EA
Bhagwat
S S
SS
Stewart
A O
AO
D000248:Adenosine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D009025:Morpholines; C115711:PD 173074; D011743:Pyrimidines; C416933:ABT 702; D000248:Adenosine Kinase