Synthesis and SAR studies of 1,4-diazabicyclo[3.2.2]nonane phenyl carbamates - subtype selective, high affinity α7 nicotinic acetylcholine receptor agonists

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 alpha 7 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 alpha 7 agonists as excellent leads for further evaluation is discussed, along with key physicochemical and pharmacokinetic data highlighting their lead potential. (C) 2009 Elsevier Ltd. All rights reserved.