[No authors listed]
The A(3) adenosine receptors (A(3) ARs), belonging to the adenosine receptor family of G-protein-coupled receptors (GPCRs), are ubiquitously expressed in a wide variety of tissues in human body, with high levels in peripheral organs and low levels in the brain. The A(3) ARs are involved in a variety of important patho-physiological processes, including modulation of cerebral and cardiac ischemic damage, inflammation, modulation of intraocular pressure, regulation of normal and tumor cell growth, and immunosuppression. Consequently, A(3) AR selective ligands may represent important pharmacological tools in the treatment of a variety of diseases. Indeed, the development of potent and selective A(3) AR ligands has been the subject of medicinal chemistry research for more than two decades. Although to date a considerable number of selective A(3) AR agonists and antagonists have been discovered, much is still to be learned about the exact function of this subtype, due to its enigmatic role in several physiological processes. In the last two decades, numerous medicinal chemistry groups have made intense efforts in searching for ideal ligands for the A(3) AR subtype. The purpose of this review is to summarize the most recent developments made in the field of selective A(3) AR ligands, which have been subdivided on the basis of their main chemical structural features. For each chemical class, attention has been focused on the SARs which determine ligand affinity and selectivity for the target subtype, and on eventually available preclinical data.
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