title: 1,4-dioxane, a suitable scaffold for the development of novel M₃ muscarinic receptor antagonists.
abstract: In this study the modulation of the pharmacological profile from agonist to antagonist was successfully obtained by replacing the methyl group in position 6 of the 1,4-dioxane scaffold of the potent M(2)/M(3) muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M(3) preferring antagonist (±)-17, which in in vivo study proved to be effective in reducing the volume-induced contractions of rat urinary bladder and was devoid of cardiovascular effects.
authors.affiliation: Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Bello
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
authors.forename: Simona
authors.initials: S
authors.lastname: Bertoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bonifazi
authors.forename: Mercedes
authors.initials: M
authors.lastname: Camalli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Campi
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
authors.forename: Rosanna
authors.initials: R
authors.lastname: Matucci
authors.forename: Marta
authors.initials: M
authors.lastname: Nesi
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000819:agonists / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology; D014554:Urination / Q000187:drug effects
chemical_list: C572355:(6,6-diphenyl-1,4-dioxan-2-yl)-N,N-dimethylmethanamine; D004146:Dioxanes; D043587:Receptor, Muscarinic M3; C025223:1,4-dioxane