Recent progress in the development of β2 adrenergic receptor agonists: a patent review (2015-2020)

ABSTRACT

Introduction

The β₂ adrenergic receptor (β₂AR) is a member of G protein-coupled receptors (GPCRs) that mediate the majority of cellular responses to external stimuli. The agonists can cause smooth muscle relaxation; therefore, many β₂AR agonists have been developed especially for the treatment of pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Many new natural and synthetic compounds have been discovered and developed as novel β₂AR agonists over the past 5 years.

Areas covered

This review offers an update for the development of β₂AR agonists in the patents published from 2015 to 2020, including new natural and synthetic compounds for the treatment of asthma and COPD. In particular, the latest patents about compounds possessing both muscarinic receptor antagonist and β₂ adrenergic receptor agonist activity are reviewed.

Expert opinion

β₂AR agonists have been developed extensively for the treatment of asthma and COPD. In the past 5 years, novel agonists from both natural sources and synthetic methods were intensively developed. Compounds possessing both muscarinic receptor antagonist and β₂AR agonist activity represent a new trend in this area because they are possibly able to act together in a synergistic fashion, therefore, relieve the symptoms of patients through two distinct mechanisms.

KEYWORDS:

• Β₂ adrenergic receptors (β₂AR)
• asthma
• chronic obstructive pulmonary disease (COPD)
• β₂AR agonists

Article highlights

• β₂AR is an important member of GPCRs that mediate various kinds of physiological processes.

• In this review, discovery and development of novel β₂AR agonists in the patents filed in the past 5 years were summarized for the treatment of the pulmonary disorders, especially asthma and COPD.

• β₂AR agonists are extensively developed and widely used in treating asthma and COPD, which are two main diseases of the respiratory system. Compounds disclosed in the patents with the best potential were chosen to illustrate their development, characteristics, and future prospects.

• Compounds possessing both muscarinic receptor antagonist and β₂AR agonist activity may be more beneficial than classical β₂AR agonists because they can act together in a synergistic fashion.

β₂AR agonists remain the first-line therapeutic drugs for both asthma and COPD today and exhibit excellent effects on improving lung functions. However, there are still challenges for better activity and higher selectivity.

Declaration of interest

M Cheng is the primary patent applicant of CN110343068, which was cited in the manuscript. The authors have no other 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 funded by the National Natural Science Foundation of China (grant number 81872752 to M.C.).