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

Expert Opin Ther Pat. 2012 Apr;22(4):369-90. doi: 10.1517/13543776.2012.669375. Epub 2012 Mar 22.

Abstract

Introduction: Adenosine exerts its effects by interacting with G-protein coupled receptors (GPCR) namely A(1), A(2A), A(2B) and A(3), 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 A(2) and A(3) 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 A(2) and A(3)ARs, 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 A(3)AR, allosteric modulation may prevent problems related to the high difference between rat and human orthosteric sites and simplify the preclinical studies on A(3)AR.

Publication types

  • Review

MeSH terms

  • Adenosine A2 Receptor Agonists / pharmacology
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Adenosine A3 Receptor Agonists / pharmacology
  • Adenosine A3 Receptor Antagonists / pharmacology
  • Drug Design
  • Humans
  • Ligands
  • Male
  • Molecular Structure
  • Patents as Topic
  • Purinergic Agents / chemistry
  • Purinergic Agents / pharmacology*
  • Receptor, Adenosine A3 / drug effects*
  • Receptor, Adenosine A3 / metabolism
  • Receptors, Adenosine A2 / drug effects*
  • Receptors, Adenosine A2 / metabolism
  • Structure-Activity Relationship

Substances

  • Adenosine A2 Receptor Agonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Agonists
  • Adenosine A3 Receptor Antagonists
  • Ligands
  • Purinergic Agents
  • Receptor, Adenosine A3
  • Receptors, Adenosine A2