A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists.

We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of alpha3- and alpha6-containing nicotinic receptors. In particular, compound 17a from this series is a potent alpha3beta4 and alpha6/4beta4 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 alpha3beta4 and alpha6/4beta4 nicotinic receptors in CNS pharmacology.

Citation

John A Lowe, Shari L DeNinno, Jotham W Coe, Lei Zhang, Scot Mente, Raymond S Hurst, Robert J Mather, Karen M Ward, Alka Shrikhande, Hans Rollema, David E Johnson, Weldon Horner, Roxanne Gorczyca, F David Tingley, Rouba Kozak, Mark J Majchrzak, Theresa Tritto, Jen Sadlier, Chris L Shaffer, Brenda Ellerbrock, Sarah M Osgood, Mary C MacDougall, Laura L McDowell. A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists. Bioorganic & medicinal chemistry letters. 2010 Aug 15;20(16):4749-52

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PMID: 20663668

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