Current Topics in Medicinal Chemistry - Volume 3, Issue 4, 2003

In this review the latest developments in ligand design for the adenosine A1 receptor are summarized. Novel series of agonists and antagonists are discussed, leading to the conclusion that ligands truly selective for the human adenosine A1 receptor are still scarce.

Adenosine's diverse physiological functions are mediated by four subtypes of receptors (A1, A2A, A2B and A3). The A1 adenosine receptor pharmacology and therapeutic application of ligands for this receptor are the subjects of this review. A1 receptors are present on the surface of cells in organs throughout the body. Actions mediated by A1 receptors include slowing of heart rate and AV nodal conduction, reduction Read More

The search for potent and selective A2A adenosine receptor agonists has been particularly fruitful in the early nineties. A series of 2-amino, 2-alkoxy, 2-alkythio-, 2-alkynyl-, and 2-alkenyl-derivatives of adenosine (Ado, 1) and N-ethylcarboxamidoadenosine (NECA, 30) have been synthesized and tested mainly on different model of rat A1 and A2A receptor subtypes. From these studies some ligands, such as CGS 21680 (33), H Read More

Due to the clearly demonstrated receptor-receptor interaction between adenosine A2A and dopamine D2 receptors in the basal ganglia, the discovery and development of potent and selective A2A adenosine receptor antagonists became, in the last ten years, an attractive field of research to discovery new drugs for the treatment of neurodegenerative disorders, such as Parkinsons disease.Different compounds ha Read More

Adenosine A2A receptors were cloned about ten years ago and are known to be well conserved among mammals. Rather selective agonists and antagonists are available. In addition, two different knock-out mice have been prepared and extensively characterized. A2A receptors are highly enriched in the basal ganglia and on cells involved in inflammatory reactions. At these sites they are likely to play physiologically importa Read More

The low affinity A2B adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven transmembrane domain G protein-coupled receptors (7TMs GPCR) and is classified by the GPCR database in the family of rhodopsin like receptors (Class A of GPCR). It has been cloned from various species, including rat and human, and its sequences are highly similar across species, ranging from 85% ident Read More

A3 Adenosine receptors (ARs) exhibit large species differences. Potent, selective agonists for rat (e.g. Cl-IB-MECA, 5) and human A3 ARs (e.g. PENECA, 17, and analogs) have been developed during the past years. Potent, selective antagonists for human A3 ARs include the imidazopurinones PSB-10 (28) and PSB-11 (29), the pyrazolotriazolopyrimidines MRE-3005F20 (38) and analogs, and the dihydropyridine Read More

The present study summarizes the biological effects elicit upon A3 adenosine receptor (A3AR) activation in normal and tumor cells. Anti-inflamatory response is mediated upon A3AR activation in neutrophils, eosinophils and macrophages via direct effect on cell degranulation or the production of anti-inflamatory cytokines. In basophils, which highly express A3AR, degranulation and mediator release upon receptor activation lead t Read More