title: Muscarinic thioligands with cyclopentane nucleus.
abstract: Some thio- and the benzoyl-derivatives of deoxamuscarine were synthesized and tested as muscarinic agonists using radioligand binding assays and functional tests. In comparison with deoxamuscarine, used as reference compound, no dimension/distance modification is tolerated for correct lipophilic pocket recognition. The substitution of the ammonium group with a sulphonium group significantly decreased muscarinic potency. The so-called 'muscarinic sub-site' accepts relatively bulky functions as long as it is bound to the cyclopentane carrier by an oxygen bridge. Esterification of this moiety increases the M2 subtype selectivity, while etherification heightens that of M3.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Piergentili
authors.forename: M
authors.initials: M
authors.lastname: Pigini
authors.forename: W
authors.initials: W
authors.lastname: Quaglia
authors.forename: S K
authors.initials: SK
authors.lastname: Tayebati
authors.forename: F
authors.initials: F
authors.lastname: Amenta
authors.forename: M
authors.initials: M
authors.lastname: Sabbatini
authors.forename: M
authors.initials: M
authors.lastname: Giannella
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003517:Cyclopentanes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008297:Male; D009116:Muscarine / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D019832:N-Methylscopolamine; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism
chemical_list: C105410:3-hydroxy-4-methyl-1-methylsulfanylmethylcyclopentane methioidide; C105411:3-hydroxy-4-methylsulfanyl-1-N,N-dimethylaminomethylcyclopentane methiodide; D003517:Cyclopentanes; D008024:Ligands; D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D009116:Muscarine; D019832:N-Methylscopolamine