Synthesis and SAR studies of 1,4-diazabicyclo[3.2.2]nonane phenyl carbamates--subtype selective, high affinity alpha7 nicotinic acetylcholine receptor agonists.

Christopher J O'Donnell, Langu Peng, Brian T O'Neill, Eric P Arnold, Robert J Mather, Steven B Sands, Alka Shrikhande, Lorraine A Lebel, Douglas K Spracklin, Frank M Nedza

Index: Bioorg. Med. Chem. Lett. 19 , 4747-51, (2009)

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Abstract

The synthesis and SAR studies about the bicyclic amine, carbamate linker and aromatic ring of a 1,4-diazabicyclo[3.2.2]nonane phenyl carbamate series of alpha7 nAChR agonists is described. The development of the medicinal chemistry strategy and SAR which led to the identification of 5 and 7aa as subtype selective, high affinity alpha7 agonists as excellent leads for further evaluation is discussed, along with key physicochemical and pharmacokinetic data highlighting their lead potential.