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

  • Bioorg Med Chem Lett. 2009 Aug 15;19(16):4747-51. doi: 10.1016/j.bmcl.2009.06.059.
Christopher J O'Donnell  1 ,  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
Affiliations
  • 1. Neuroscience Medicinal Chemistry, Pfizer Global Research & Development, Groton, CT 06340, United States. [email protected]
PMID: 19576766 DOI: 10.1016/j.bmcl.2009.06.059
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.