A novel series of [3.2.1] azabicyclic biaryl ethers as α3β4 and α6/4β4 nicotinic receptor agonists

We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of α3- and α6-containing nicotinic receptors. In particular, compound 17a from this series is a potent α3β4 and α6/4β4 receptor agonist in terms of both binding and functional activity. Compound 17a also shows potent in vivo activity in CNS-mediated animal models that are sensitive to antipsychotic drugs. Compound 17a may thus be a useful tool for studying the role of α3β4 and α6/4β4 nicotinic receptors in CNS pharmacology.

Graphical abstractWe report the discovery of compound 17a, a potent α3β4 and α6/4β4 receptor agonist.Figure optionsDownload full-size imageDownload as PowerPoint slide