title: Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.
abstract: The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]quinuclidinyl benzilate. Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom. Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated. A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex, U.K.
authors.forename: H J
authors.initials: HJ
authors.lastname: Wadsworth
authors.forename: S M
authors.initials: SM
authors.lastname: Jenkins
authors.forename: B S
authors.initials: BS
authors.lastname: Orlek
authors.forename: F
authors.initials: F
authors.lastname: Cassidy
authors.forename: M S
authors.initials: MS
authors.lastname: Clark
authors.forename: F
authors.initials: F
authors.lastname: Brown
authors.forename: G J
authors.initials: GJ
authors.lastname: Riley
authors.forename: D
authors.initials: D
authors.lastname: Graves
authors.forename: J
authors.initials: J
authors.lastname: Hawkins
authors.forename: C B
authors.initials: CB
authors.lastname: Naylor
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D004563:Electrochemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010095:Oxotremorine / Q000378:metabolism; D010277:Parasympathomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D013777:Tetrazoles; D014230:Triazoles; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate