From pyrrolidinyl-benzodioxane to pyrrolidinyl-pyridodioxanes, or from unselective antagonism to selective partial agonism at ?4?2 nicotinic acetylcholine receptor
Each of the four aromatic eCH¼ of (S,R)-2-pyrrolidinyl-1,4-benzodioxane [(S,R)-6] and of its epimer at the dioxane stereocenter (S,S)-6, previously reported as a4b2 nAChR ligands, was replaced with nitrogen. The resulting four diastereoisomeric pairs of pyrrolidinyl-pyridodioxanes were studied for the nicotinic affinity and activity at a4b2, a3b4 and a7 nAChR subtypes and compared to their common carbaisostere.