These ligands incorporate key elements associated with contemporary nicotinic pharmacophores, [4] namely a basic amine (protonated at physiological pH) and a π-system incorporating a hydrogen bond acceptor (the pyridyl ring of 1 and the ketone oxygen of 2). These two pharmacophore elements must be maintained in the appropriate arrangement to interact with the nAChR, and the rigid bicycle associated with 1 and 2 provides the scaffold ...
