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

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• A_2BAR antagonists
• A_2A/A_2BAR antagonists
• inflammatory pathologies
• cancer

Article highlights

•A2B adenosine receptor (A2BAR) plays a crucial role in pathophysiologic conditions associated with high adenosine release.

• A2BAR plays a specific role in many pathologies including cancer and asthma.

• The discovery of new molecule classes able to antagonize A2BAR or A2B/A2AARs opened a new perspective in pharmacotherapy.

• Unfortunately, only few A2BAR antagonists reached the clinical trials.

This box summarizes key points contained in the article.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.