Adenosine A2A receptors are members of the G protein-coupled receptor family and mediate multiple physiological effects of adenosine, both at the central nervous system (CNS) and at peripheral tissues, by activating several pathways or interacting with other receptors or proteins. Increasing evidence relate A2A receptors with pharmacological stress testing, neurodegenerative disorders (such as Parkinson's disease) and inflammation, renewing the interest in these receptors, increasingly viewed as promising therapeutic targets.

Series of agonists and antagonists have been developed by medicinal chemistry artwork either by structure activity relationship (SAR) or quantitative structure activity relationship (QSAR) studies. These studies have allowed identification of the structural and electrostatic requirements for high affinity A2A receptor binding and, therefore, contributing to the rational design of A2A receptor ligands. Additional rational chemical modifications of the existing A2A receptor ligands may further improve their affinity/selectivity.

The purpose of this review is to analize and summarize aspects related to the medicinal chemistry of A2A receptor ligands, their present and potencial therapeutic applications by exploring the molecular structure and physiological and pathophysiological roles of A2A receptors.