title: 3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.
abstract: A novel series of 3-substituted-8-aryl-[1,2,4]-triazolo[5,1-i]purin-5-amine analogs related to Sch 58261 was synthesized in order to identify potent adenosine A(2A) receptor antagonists with improved selectivity over the A(1) receptor, physiochemical properties, and pharmacokinetic profiles as compared to those of Sch 58261. As a result of structural modifications, numerous analogs with excellent in vitro binding affinities and selectivities were identified. Moreover, compound 27 displayed both superior in vitro and highly promising in vivo profiles.
authors.affiliation: CV & CNS Departments of Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Silverman
authors.forename: John P
authors.initials: JP
authors.lastname: Caldwell
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kiselgof
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Matasi
authors.forename: Deen B
authors.initials: DB
authors.lastname: Tulshian
authors.forename: Leyla
authors.initials: L
authors.lastname: Arik
authors.forename: Carolyn
authors.initials: C
authors.lastname: Foster
authors.forename: Rosalia
authors.initials: R
authors.lastname: Bertorelli
authors.forename: Angela
authors.initials: A
authors.lastname: Monopoli
authors.forename: Ennio
authors.initials: E
authors.lastname: Ongini
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D011687:Purines; D011743:Pyrimidines; D014230:Triazoles