Papers of the Week

Opioids are commonly prescribed for the treatment of neuropathic pain; however, their high rates of physical dependency and addiction raise concern. Given their adverse side effects, there is a need for new therapeutics that target non-opioid receptors. GPR183 (Epstein-Barr induced gene 2, EBI2) is a G-protein coupled receptor (GPCR) that plays a role in the transduction of neuropathic pain. SAE-14 is a novel molecule that is able to antagonize, or inhibit GPR183; thus, preventing the transmission of pain. To gain a better understanding of which substituents improve the binding between SAE-14 and GPR-183, it is necessary to synthesize several analogs of the molecule. We have developed a structure-activity-relationship for GPR183 antagonism and the results from this gives a better understanding of the functional groups that are necessary for GPR183 antagonism and improve to the compound's potential therapeutic for neuropathic pain treatment.