Therapeutic potential of A₂ and A₃ adenosine receptor: a review of novel patented ligands

Abstract

Introduction: Adenosine exerts its effects by interacting with G-protein coupled receptors (GPCR) namely A₁, A_2A, A_2B and A₃, respectively. These are involved in several diseases, for example and most importantly, Parkinson's disease, ischemia and inflammation. There is high interest in the development of potent and selective ligands for these adenosine receptor (AR) subtypes, primarily for their therapeutic potential but also as pharmacological tools in receptor studies.

Areas covered: This paper concentrates on reviewing the therapeutic potential of A₂ and A₃ ARs, which represent the most interesting subtypes of recent years. A general description of each receptor is reported with novel agonist and antagonist structures, patented in 2008 – 2011. PubMed and Free Patents Online databases were principally used to collect all the material.

Expert opinion: In the past years, by modulating A₂ and A₃ARs, several new possible therapeutic applications were discovered. For this reason, research concerning AR ligands is still of great interest. In particular, few potent and selective A_2B agonists and antagonists are actually reported and a clear SAR (structure–activity relationship) profile lacks for this AR subtype. At the A₃AR, allosteric modulation may prevent problems related to the high difference between rat and human orthosteric sites and simplify the preclinical studies on A₃AR.

Keywords::

• A_2A receptor
• A_2B receptor
• A₃ receptor
• adenosine receptors
• agonists
• allosteric modulators
• antagonists
• GPCR

Notes

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