In silico identification of a biarylamine acting as agonist at human β adrenoceptors and exerting BRL37344-like effects on mouse metabolism.

Human β-adrenoceptor (βAR) agonists were considered potential agents for the treatment of metabolic disorders. However, compounds tested as βAR ligands have shown marked differences in pharmacological profile in rodent and human species, although these compounds remain attractive as they were successfully repurposed for the therapy of urinary incontinence. In this work, some biarylamine compounds were designed and tested in silico as potential βAR agonists on 3-D models of mouse or human βARs.

Cell-based assays and molecular dynamics analysis of a boron-containing agonist with different profiles of binding to human and guinea pig beta2 adrenoceptors.

The design of beta2 adrenoceptor (βAR) agonists is attractive because of their wide-ranging applications in medicine, and the details of agonist interactions with βAR are interesting because it is considered a prototype for G-protein coupled receptors. Preclinical studies for agonist development have involved biological assays with guinea pigs due to a similar physiology to humans. Boron-containing Albuterol derivatives (BCADs) designed as bronchodilators have improved potency and efficacy compared with their boron-free precursor on guinea pig βARs (gpβARs), and two of the BCADs (BR-AEA and boronterol) conserve these features on cells expressing human βARs (hβARs).