The discovery and synthesis of novel adenosine receptor (A 2A) antagonists

• Published in: Bioorganic & medicinal chemistry letters 2005-03, Vol.15 (5), p.1333-1336
• Main Authors: Matasi, Julius J., Caldwell, John P., Hao, Jinsong, Neustadt, Bernard, Arik, Leyla, Foster, Carolyn J., Lachowicz, Jean, Tulshian, Deen B.
• Format: Article
• Language: English
• Subjects: Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Adenosine receptor; Antagonist; Antiparkinson Agents - chemical synthesis; Antiparkinson Agents - classification; Antiparkinson Agents - pharmacology; Arylindenopyrimidines; Biological and medical sciences; Drug Evaluation, Preclinical; Heterocyclic Compounds, 3-Ring - chemical synthesis; Heterocyclic Compounds, 3-Ring - pharmacology; Medical sciences; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.01.019

The structure–activity relationship investigation using 1 as a template led to the identification of a novel class of compounds as potent and selective antagonists of the A 2A receptor. Compound 26 was identified to be the most potent A 2A antagonist ( K i = 0.8 nM) with 100-fold selectivity over the A 1 receptor. 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 A 1 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 ( K i = 0.8 nM) with 100-fold selectivity over the A 1 adenosine receptor.