Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB2 Receptor

Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB2 receptor. These compounds selectively target CB2 versus CB1 receptors. Their binding mode was studied by molecular dynamic simulations and site¿directed mutagenesis.This work was supported by the MICIU/FEDER (RTI2018- 095544-B-I00, PID2019-109240RB-I00, SAF2017-84117-R), and by the CSIC (PIE-201580E033). P.M. is grateful to the CM program “Atraccijn de Talento Investigador” number 2018-T2/ BMD-1081