Synthesis and Structure-Activity Relationship of SAE-14 Analogs as G-Protein Coupled Receptor 183 Antagonists

Abstract ID 54221 Poster Board 553 The therapeutic management of neuropathic pain (NP) targets opioid receptors to modulate their signal processes. Currently, the most effective therapeutic analgesia is opioids to manage the long-term treatment of NP, and these unfortunately have associated side effects including addiction and physical dependencies. GPR183 (Epstein-Barr induced gene 2, EBI2), a non-opioid G-protein coupled receptor (GPCR) revealed to be involved in the pathway of NP generation. SAE-14, a novel small molecule, is a lead compound that was shown to antagonize GPR183 and is active in vivo in a chronic constriction model of neuropathic pain. It is necessary to optimize the pharmacophores of SAE-14 to enhance its binding interactions with GPR183. Therefore, we investigated a structural activity relationship of SAE-14, to uncover improved functional groups that would augment its antagonistic activity.