title: Synthesis, affinity profile, and functional activity of muscarinic antagonists with a 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine structure.
abstract: Starting from a previously studied muscarinic ligand, characterized by a 1,3-oxathiolane nucleus, a new series of muscarinic antagonists were designed by increasing the stereochemical complexity of the molecules. A small library of enantiomeric and diastereomeric 2,2-diphenyl- and 2-cyclohexyl-2-phenyl substituted compounds was thus obtained. All the tested compounds show a high affinity toward cloned human muscarinic hm1-hm5 receptors expressed in CHO cells and a good antagonistic activity on functional assays, with a modest selectivity on rabbit vas deferens.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy. silvia.dei@unifi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.forename: Cristina
authors.initials: C
authors.lastname: Bellucci
authors.forename: Michela
authors.initials: M
authors.lastname: Buccioni
authors.forename: Marta
authors.initials: M
authors.lastname: Ferraroni
authors.forename: Luca
authors.initials: L
authors.lastname: Guandalini
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Martini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marucci
authors.forename: Rosanna
authors.initials: R
authors.lastname: Matucci
authors.forename: Marta
authors.initials: M
authors.lastname: Nesi
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Romanelli
authors.forename: Serena
authors.initials: S
authors.lastname: Scapecchi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D011976:Receptors, Muscarinic; D013876:Thiophenes