A 2A adenosine receptor agonists, antagonists, inverse agonists and partial agonists.

The Gs-coupled A2A adenosine receptor (A2A AR) has been explored extensively as a pharmaceutical target, which has led to numerous clinical trials. However, only one selective A2A AR agonist (regadenoson, Lexiscan) and one selective A2A AR antagonist (istradefylline, Nouriast) have been approved by the FDA, as a pharmacological agent for myocardial perfusion imaging (MPI) and as a cotherapy for Parkinson's disease (PD), respectively. Adenosine is widely used in MPI, as Adenoscan. Despite numerous unsuccessful clinical trials, medicinal chemical activity around A2A AR ligands has accelerated recently, particularly through structure-based drug design. New drug-like A2A AR antagonists for PD and cancer immunotherapy have been identified, and many clinical trials have ensued. For example, imaradenant (AZD4635), a compound that was designed computationally, based on A2A AR X-ray structures and biophysical mapping. Mixed A2A AR/A2B AR antagonists are also hopeful for cancer treatment. A2A AR antagonists may also have potential as neuroprotective agents for treatment of Alzheimer's disease.