Abstract::Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition defined by
persistent bronchitis, emphysema, and structural remodelling. The number of cases has risen globally;
however, limited viable remedies exist. It is linked to airway blockage, oxidative stress, chronic
conditions, inflammation, excessive mucus production, and increased autophagy and cellular senescence.
Beta-2 adrenergic receptors (β2-ARs) play a significant role in both the aetiology and management
of COPD. Beta-2 agonists (particularly long-acting beta-agonists, or LABAs) are preferable
in COPD therapy due to their powerful bronchodilation, rapid onset, prolonged duration, and
potential synergistic effects with other medications. They are well-tolerated and effective in improving
the quality of life and reducing exacerbations, making them an essential component of COPD
treatment. Currently, there are fewer bronchodilators that have been found to be effective. This leads
to an exploration of novel, long-acting, and ultra-long-acting drugs for the management of COPD.
This article provides an extensive overview of natural β2 agonists. The current study emphasizes the
rational development of lead candidates, including trantinterol, isopropyl, tert-butyl, and heterocyclic
ring 2-amino-2-phenylethanol derivatives, 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-
benzoxazine-3(4H)-one derivatives (non-substituted, methyl-substituted, dimethyl-substituted), 5-
(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one analogues, indacaterol analogues, saligenin
antedrugs, and saligenin alkoxyalkylphenyl sulfonamide derivatives, accompanied by molecular
docking studies.This paper also highlights numerous structure-activity relationship investigations
and various novel β2 agonists currently in clinical trials and patents. The present review will significantly
aid in fostering the research of COPD.
