“Photo‐Adrenalines”: Photoswitchable β₂‐Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling

Abstract

β₂ -adrenergic receptor (β₂ -AR) agonists are used for the treatment of asthma and chronic obstructive pulmonary disease, but also play a role in other complex disorders including cancer, diabetes and heart diseases. As the cellular and molecular mechanisms in various cells and tissues of the β₂ -AR remain vastly elusive, we developed tools for this investigation with high temporal and spatial resolution. Several photoswitchable β₂ -AR agonists with nanomolar activity were synthesized. The most potent agonist for β₂ -AR with reasonable switching is a one-digit nanomolar active, trans-on arylazopyrazole-based adrenaline derivative and comprises valuable photopharmacological properties for further biological studies with high structural accordance to the native ligand adrenaline.