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Probing Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices via Laser Flash Photolysis of Photoactivatable Nicotine
Published on: January 25, 2019
Novel nicotinic acetylcholine receptor agonists containing carbonyl moiety as a hydrogen bond acceptor
Anatoly A Mazurov1, David C Kombo, Srinivasa Akireddy
1Targacept, Inc., 100 North Main Street, Winston-Salem, NC 27101, USA. galana99@yahoo.com
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).
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