3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.
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.
Silverman
Lisa S
LS
CV & CNS Departments of Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Caldwell
John P
JP
Greenlee
William J
WJ
Kiselgof
Eugenia
E
Matasi
Julius J
JJ
Tulshian
Deen B
DB
Arik
Leyla
L
Foster
Carolyn
C
Bertorelli
Rosalia
R
Monopoli
Angela
A
Ongini
Ennio
E
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*
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