title: Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine.
abstract: A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M(1)-M(3) receptor subtypes. The most interesting compound was (cis,trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole oxalate (6), which is equipotent with Pirenzepine on rabbit vas deferens (M(1)-putative) but shows a better selectivity profile.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, Via S. Agostino, 1, 62032 Camerino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
authors.forename: Francesco
authors.initials: F
authors.lastname: Gentili
authors.forename: Francesca
authors.initials: F
authors.lastname: Ghelfi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marucci
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004148:Dioxolanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D010070:Oxalates / Q000737:chemistry; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
chemical_list: C087747:2,2-diphenyl-(1,3)-dioxolan-4-ylmethyl(dimethyl)amine methiodide; D001643:Bridged Bicyclo Compounds; D004148:Dioxolanes; D006847:Hydrocarbons, Iodinated; D018727:Muscarinic Antagonists; D010070:Oxalates; D011976:Receptors, Muscarinic