A patent review of adenosine A_2B receptor antagonists (2016-present)

A_2B adenosine receptor (A_2BAR) plays a crucial role in pathophysiologic conditions associated with high adenosine release, typical of airway inflammatory pathologies, gastrointestinal disorders, cancer, asthma, type 2 diabetes, and atherosclerosis. In some pathologies, simultaneous inactivation of A_2A and A_2BARs is desirable to have a synergism of action that leads to a greater efficacy of the pharmacological treatment and less side effects due to the dose of drug administered. In this context, it is strongly required to identify molecules capable of selectively antagonizing A_2BAR or A_2A/A_2BARs.

The review provides a summary of patents, published from 2016 to present, on chemicals and their clinical use. In this paper, information on the biological activity of representative structures of recently developed A_2B or A_2A/A_2B receptor ligands is reported.

Among the four P1 receptors, A_2BAR is the most inscrutable and the least studied until a few years ago, but its involvement in various inflammatory pathologies has recently made it a pharmacological target of high interest. Many efforts by the academy and pharmaceutical companies have been made to discover potential A_2BAR and A_2A/A_2BARs drugs. Although several compounds have been synthesized only a few molecules have entered clinical trials.