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

Julius J Matasi; John P Caldwell; Jinsong Hao; Bernard Neustadt; Leyla Arik; Carolyn J Foster; Jean Lachowicz; Deen B Tulshian

doi:10.1016/j.bmcl.2005.01.019

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

Bioorg Med Chem Lett. 2005 Mar 1;15(5):1333-6. doi: 10.1016/j.bmcl.2005.01.019.

Authors

Julius J Matasi¹, John P Caldwell, Jinsong Hao, Bernard Neustadt, Leyla Arik, Carolyn J Foster, Jean Lachowicz, Deen B Tulshian

Affiliation

¹ Department of Medicinal Chemistry-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.

PMID: 15713381
DOI: 10.1016/j.bmcl.2005.01.019

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.

MeSH terms

Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Antagonists*
Antiparkinson Agents / chemical synthesis*
Antiparkinson Agents / classification
Antiparkinson Agents / pharmacology
Drug Evaluation, Preclinical
Heterocyclic Compounds, 3-Ring / chemical synthesis*
Heterocyclic Compounds, 3-Ring / pharmacology
Molecular Structure
Structure-Activity Relationship

Substances

Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Antagonists
Antiparkinson Agents
Heterocyclic Compounds, 3-Ring