title: Design, synthesis and structure-activity relationship of N-substituted tropane muscarinic acetylcholine receptor antagonists.
abstract: A novel series of N-substituted tropane derivatives was characterized as potent muscarinic acetylcholine receptor antagonists (mAChRs). Kinetic washout studies showed that the N-endosubstituted analog 24 displayed much slower reversibility at mAChRs than the methyl-substituted parent molecule darotropium. In addition, it was shown that this characteristic appeared to translate into enhanced which duration of action in a mouse model of bronchonstriction.
authors.affiliation: GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Dramane I
authors.initials: DI
authors.lastname: Lainé
authors.forename: Hongxing
authors.initials: H
authors.lastname: Yan
authors.forename: Haibo
authors.initials: H
authors.lastname: Xie
authors.forename: Roderick S
authors.initials: RS
authors.lastname: Davis
authors.forename: Jeremy
authors.initials: J
authors.lastname: Dufour
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Widdowson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Palovich
authors.forename: Zehong
authors.initials: Z
authors.lastname: Wan
authors.forename: James J
authors.initials: JJ
authors.lastname: Foley
authors.forename: Dulcie B
authors.initials: DB
authors.lastname: Schmidt
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hunsberger
authors.forename: Miriam
authors.initials: M
authors.lastname: Burman
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Bacon
authors.forename: Edward F
authors.initials: EF
authors.lastname: Webb
authors.forename: Mark A
authors.initials: MA
authors.lastname: Luttmann
authors.forename: Michael
authors.initials: M
authors.lastname: Salmon
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sarau
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Umbrecht
authors.forename: Philip S
authors.initials: PS
authors.lastname: Landis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Peck
authors.forename: Jakob
authors.initials: J
authors.lastname: Busch-Petersen
mesh_terms: D000818:Animals; D001982:Bronchial Diseases / Q000188:drug therapy; D015195:Drug Design; D051379:Mice; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D014326:Tropanes