Azologization yields light-activated β1-adrenoceptor agonists with an inactive trans form
- Prior photoswitchable β-adrenoceptor agonists lacked a fully inactive trans isomer that light could reversibly switch on.
- Azologization of two known agonists, BI-167107 and Cimaterol, produced a series of photoswitchable β1-AR ligands that activate the receptor selectively upon illumination.
- The light-on compounds respond to UV and visible light and differ in thermal relaxation kinetics and efficacy.
- Modifying the core scaffold allows photochemical and pharmacological properties to be tuned.
💡 Points Based on the abstract
Starting from BI-167107 and Cimaterol is the smart move: both are well-validated agonist chemotypes with known binding poses, so inserting the azo unit is a bioisosteric swap rather than blind scaffold hopping. The open question is how the trans form stays truly silent when the parent ligands are so potent. Tunable relaxation and efficacy also make this a usable SAR set for GPCR activation kinetics, not just a tool compound.