title: Novel nicotinic acetylcholine receptor agonists containing carbonyl moiety as a hydrogen bond acceptor.
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).
authors.affiliation: Targacept, Inc., 100 North Main Street, Winston-Salem, NC 27101, USA. galana99@yahoo.com
authors.forename: Anatoly A
authors.initials: AA
authors.lastname: Mazurov
authors.forename: David C
authors.initials: DC
authors.lastname: Kombo
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Akireddy
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Murthy
authors.forename: Terry A
authors.initials: TA
authors.lastname: Hauser
authors.forename: Kristen G
authors.initials: KG
authors.lastname: Jordan
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gatto
authors.forename: Daniel
authors.initials: D
authors.lastname: Yohannes
mesh_terms: D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D011725:Pyridines; D011978:Receptors, Nicotinic; C023666:pyridine