Novel nicotinic acetylcholine receptor agonists containing carbonyl moiety as a hydrogen bond acceptor

  • Bioorg Med Chem Lett. 2013 Jul 1;23(13):3927-34. doi: 10.1016/j.bmcl.2013.04.058.
Anatoly A Mazurov  1 ,  David C Kombo ,  Srinivasa Akireddy ,  Srinivasa Murthy ,  Terry A Hauser ,  Kristen G Jordan ,  Gregory J Gatto ,  Daniel Yohannes
Affiliations
  • 1. Targacept, Inc., 100 North Main Street, Winston-Salem, NC 27101, USA. [email protected]
PMID: 23692872 DOI: 10.1016/j.bmcl.2013.04.058
Abstract

A novel series of α4β2 nAChR agonists lacking common pyridine or its bioisosteric heterocycle have been disclosed. Essential pharmacophoric elements of the series are exocyclic carbonyl moiety as a hydrogen bond acceptor and secondary amino group within diaza- or azabicyclic scaffold. Computer modeling studies suggested that molecular shape of the ligand also contributes to promotion of agonism. Proof of concept for improving working memory performance in a novel object recognition task has been demonstrated on a representative of the series, 3-propionyl-3,7-diazabicyclo[3.3.0]octane (34).