Synthesis and binding affinity at α4β2 and α7 nicotinic acetylcholine receptors of new analogs of epibatidine and epiboxidine containing the 7-azabicyclo[2.2.1]hept-2-ene ring system.

摘要: A group of novel racemic nicotinic ligands structurally related to epibatidine or epiboxidine [(±)-10-(±)-17] was synthesized through a palladium-catalyzed cross-coupling between the appropriate vinyl triflate and range organometallic heterocycles. The target compounds were evaluated for binding affinity at α4β2 α7 neuronal receptors (nAChRs). set 3-pyridinyl derivatives (±)-10, (±)-11 (±)-12 exhibited an nAChR subtype in subnanomolar (K(i) values 0.20, 0.40 0.50nM, respectively) behaved as versus selective ligands. Interestingly, epiboxidine-related dimethylammonium iodide (±)-17, which retained good (K(i)=13.30nM), tightly bound also (K(i)=1.60nM), thus displaying reversal trend among reference new under investigation.