The discovery and synthesis of novel adenosine receptor (A(2A)) antagonists.
In high throughput screening of our file compounds, a novel structure 1 was identified as a potent A(2A) receptor antagonist with no selectivity over the A1 adenosine receptor. The structure-activity relationship investigation using 1 as a template lead to identification of a novel class of compounds as potent and selective antagonists of A(2A) adenosine receptor. Compound 26 was identified to be the most potent A(2A) receptor antagonist (Ki = 0.8 nM) with 100-fold selectivity over the A1 adenosine receptor.
Matasi
Julius J
JJ
Department of Medicinal Chemistry-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Caldwell
John P
JP
Hao
Jinsong
J
Neustadt
Bernard
B
Arik
Leyla
L
Foster
Carolyn J
CJ
Lachowicz
Jean
J
Tulshian
Deen B
DB
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D006575:Heterocyclic Compounds, 3-Ring