title: Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines.
abstract: 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.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-1310, USA. bernard.neustadt@spcorp.com
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Neustadt
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Hao
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stamford
authors.forename: Carolyn
authors.initials: C
authors.lastname: Foster
authors.forename: Leyla
authors.initials: L
authors.lastname: Arik
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Rosalia
authors.initials: R
authors.lastname: Bertorelli
authors.forename: Silva
authors.initials: S
authors.lastname: Fredduzzi
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Varty
authors.forename: Mary
authors.initials: M
authors.lastname: Cohen-Williams
authors.forename: Kwokei
authors.initials: K
authors.lastname: Ng
mesh_terms: 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
chemical_list: 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