title: The discovery and synthesis of novel adenosine receptor (A(2A)) antagonists.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Matasi
authors.forename: John P
authors.initials: JP
authors.lastname: Caldwell
authors.forename: Jinsong
authors.initials: J
authors.lastname: Hao
authors.forename: Bernard
authors.initials: B
authors.lastname: Neustadt
authors.forename: Leyla
authors.initials: L
authors.lastname: Arik
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Foster
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
authors.forename: Deen B
authors.initials: DB
authors.lastname: Tulshian
mesh_terms: 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
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D006575:Heterocyclic Compounds, 3-Ring