title: Preparation and characterization of N-(3-pyridinyl) spirocyclic diamines as ligands for nicotinic acetylcholine receptors.
abstract: Several N-pyridin-3-yl spirobicyclic diamines, designed as conformationally restricted analogs of tebanicline (ABT-594), were synthesized as novel ligands for nicotinic acetylcholine receptors (nAChR). The spirocyclic compounds exhibited weaker binding affinity, than other constrained analogs in accord with a pharmacophore model. Nevertheless, some (1a, 1b) possessed (partial) agonist potencies comparable to nicotine at the alpha4beta2 subtype, but with greatly improved selectivity relative to the alpha3beta4* nAChR.
authors.affiliation: Neuroscience Research, Abbott Laboratories, Department R47W, 100 Abbott Park Rd., Building AP9A, Abbott Park, IL 60064-6117, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Sippy
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: William H
authors.initials: WH
authors.lastname: Bunnelle
authors.forename: Charles W
authors.initials: CW
authors.lastname: Hutchins
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schrimpf
mesh_terms: D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003959:Diamines / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C109763:5-(2-azetidinylmethoxy)-2-chloropyridine; D001384:Azetidines; D003959:Diamines; D008024:Ligands; D011725:Pyridines; D011978:Receptors, Nicotinic