Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines.
Antagonism of the adenosine A(2a) receptor offers great promise in the treatment of Parkinson's disease. In the course of exploring pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonists, which led to clinical candidate SCH 420814, we prepared 1,2,4-triazolo[1,5-c]pyrimidines with potent and selective (vs A(1)) A(2a) antagonist activity, including oral activity in the rat haloperidol-induced catalepsy model. Structure-activity relationships and plasma levels are described for this series.
Neustadt
Bernard R
BR
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-1310, USA. bernard.neustadt@spcorp.com
Liu
Hong
H
Hao
Jinsong
J
Greenlee
William J
WJ
Stamford
Andrew W
AW
Foster
Carolyn
C
Arik
Leyla
L
Lachowicz
Jean
J
Zhang
Hongtao
H
Bertorelli
Rosalia
R
Fredduzzi
Silva
S
Varty
Geoffrey
G
Cohen-Williams
Mary
M
Ng
Kwokei
K
D058917:Adenosine A2 Receptor Antagonists; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002375:Catalepsy; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006220:Haloperidol / Q000494:pharmacology; D008956:Models, Chemical; D010300:Parkinson Disease / Q000188:drug therapy*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine; D006220:Haloperidol