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 CB 2 receptor. These compounds selectively target CB 2 versus CB 1 receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis.