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

The Gs-coupled A adenosine receptor (AAR) has been explored extensively as a pharmaceutical target, which has led to numerous clinical trials. However, only one selective AAR agonist (regadenoson, Lexiscan) and one selective AAR 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 AAR ligands has accelerated recently, particularly through structure-based drug design. New drug-like AAR 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 AAR X-ray structures and biophysical mapping. Mixed AAR/AAR antagonists are also hopeful for cancer treatment. AAR antagonists may also have potential as neuroprotective agents for treatment of Alzheimer's disease.