Non-Nucleoside Agonists of the Adenosine Receptors: An Overview

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 12; no. 4; p. 150
• Main Authors: Dal Ben, Diego, Lambertucci, Catia, Buccioni, Michela, Martí Navia, Aleix, Marucci, Gabriella, Spinaci, Andrea, Volpini, Rosaria
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.10.2019; MDPI
• Subjects: Adenosine; adenosine receptor agonists; adenosine receptors; Biological activity; drug discovery; Drug dosages; Heart failure; Heart rate; Kinases; ligand–target interaction; non-nucleoside agonists; Proteins; purinergic receptors; pyridine derivatives; pyrimidine derivatives; Review; pyrimidine derivatives; purinergic receptors; drug discovery; adenosine receptors; pyridine derivatives; adenosine receptor agonists; non-nucleoside agonists; ligand–target interaction
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph12040150

Potent and selective adenosine receptor (AR) agonists are of pharmacological interest for the treatment of a wide range of diseases and conditions. Among these derivatives, nucleoside-based agonists represent the great majority of molecules developed and reported to date. However, the limited availability of compounds selective for a specific AR subtype (i.e., A AR) and a generally long and complex synthetic route for largely substituted nucleosides are the main drawbacks of this category of molecules. Non-nucleoside agonists represent an alternative set of compounds able to stimulate the AR function and based on simplified structures. This review provides an updated overview on the structural classes of non-nucleoside AR agonists and their biological activities, with emphasis on the main derivatives reported in the literature. A focus is also given to the synthetic routes employed to develop these derivatives and on molecular modeling studies simulating their interaction with ARs.