(537.25) Structure Activity Relationship and Biological Evaluation of Small Molecule Antagonists for G-Protein Coupled Receptor Associated with Neuropathic Pain

Poster Board Number: B101

Israel Olayide (Saint Louis University), Kathryn Braden (Saint Louis University), Nicholas Latzo (Saint Louis University), Daniela Salvemini (Saint Louis University), Christopher Arnatt (Saint Louis University)

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.

lt;bgt;lt;/bgt;Supported by funds from Dr. Salvemini and Dr. Arnatt and T32 GM008306-01 training grant (KB)