A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling. Keywords: azo compounds; chemokine receptor; efficacy photoswitching; G protein-coupled receptors; photopharmacology; Introduction Photopharmacology is an emerging discipline at the interface

• substituent to the binding site of the receptor [24]. In order to obtain an efficacy photoswitching, we opted for replacing the biaryl moiety for an azobenzene in an azologization approach (Figure 1D) with the expectation that the isomerization of the azobenzene would provide changes in 3D shape that are

• efficacy photoswitching (Figure 3). To confirm this for subseries 4, the analogues of 4d with the bromine on the meta and para position (5b and 5c, respectively) were also synthesized. The synthetic route (Scheme 1) utilized 10c and 3- and 4-bromonitrosobenzene (11k,l) to form azobenzenes 15b,c, which were