title: Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes.
abstract: A series of epiboxidine homologues, 2- and 3-isoxazole substituted 8-azabicyclo[3.2.1]octane derivatives was synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors in [(3)H]cytisine labeled rat brain. The 2beta-isoxazolyl-8-azabicyclo[3.2.1]octane 9b (K(i)=3 nM) was the most potent compound of the series with a binding affinity twice that of nicotine. The 3beta-isoxazolyl-8-azabicyclo[3.2.1]octane 15b (K(i)=148 nM) exhibited moderate affinity while the corresponding 2alpha- and 3alpha-isomers exhibited micromolar binding affinity.
authors.affiliation: Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Sari
authors.initials: S
authors.lastname: Izenwasser
authors.forename: Chunming
authors.initials: C
authors.lastname: Zhang
authors.forename: Suhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Dean
authors.initials: D
authors.lastname: Wade
authors.forename: Mark L
authors.initials: ML
authors.lastname: Trudell
mesh_terms: D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D009795:Octanes / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D009795:Octanes; D011978:Receptors, Nicotinic