Sulfonium as a Surrogate for Ammonium: A New alpha 7 Nicotinic Acetylcholine Receptor Partial Agonist with Desensitizing Activity

摘要

Weak partial agonists that promote a desensitized state of the alpha 7 nicotinic acetylcholine receptor (nAChR) have been associated with anti-inflammatory effects. Exemplar compounds feature a tertiary or quaternary ammonium group. We report the synthesis, structure, and electrophysiological evaluation of 1-ethyl-4-phenylthiomorpholin-1-ium triflate, a weak partial agonist with a sulfonium isostere of the ammonium pharmacophore. These results offer new insights in understanding nAChR ligand interactions and provide a new chemical space to target the alpha 7 nAChR.