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

Abstract β 2 ‐adrenergic receptor (β 2 ‐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 β 2 ‐AR remain vastly elusive, we developed tools for this investigation with high temporal and spatial resolution. Several photoswitchable β 2 ‐AR agonists with nanomolar activity were synthesized. The most potent agonist for β 2 ‐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.