Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based adenosine kinase inhibitors.
Three new approaches have been tested to modify existing pyridopyrimidine and alkynylpyrimidine classes of nonnucleoside adenosine kinase inhibitors 2 and 3. 4-Amino-substituted pteridines 8a-e were generally less active than corresponding 5- and 6-substituted pyridopyrimidines 2. Pyrazolopyrimidine 13c with IC(50)=7.5 nM was superior to its open chain alkynylpyrimidine analog 13g (IC(50)=22 nM) while pyrrolopyrimidines such as 17a were inactive.
Gomtsyan
Arthur
A
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. arthur.r.gomtsyan@abbott.com
Didomenico
Stanley
S
Lee
Chih-Hung
CH
Stewart
Andrew O
AO
Bhagwat
Shripad S
SS
Kowaluk
Elizabeth A
EA
Jarvis
Michael F
MF
D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011621:Pteridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011621:Pteridines; D011720:Pyrazoles; D011743:Pyrimidines; D000248:Adenosine Kinase