Diazaspirocyclic compounds as selective ligands for the α4β2 nicotinic acetylcholine receptor.

Abstract Diazaspirocyclic ligands have been synthesized in four steps as selective α4β2 nicotinic acetylcholine receptor antagonists. Structural assignment of 1-(pyridin-3-yl)-2-spiropyrrolidino-3,2′-1-azabiclo[2.2.1]heptane 2 , was confirmed using a combination of NMR experiments on a key intermediate, spirolactam 9 . All three target compounds synthesized in this diazaspirocyclic series exhibited high affinity ( K i K i  >500 nM).