Muscarinic antagonists with multiple stereocenters: Synthesis, affinity profile and functional activity of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine sulfoxide derivatives.
Completing a long-lasting research on 1,3-oxathiolane muscarinic ligands, we have synthesized a set of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide derivatives, containing three or four stereogenic centers. In general the compounds are very potent antagonists even if, unlike the corresponding agonists, they show modest subtype selectivity.
Dei
Silvia
S
Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi (HeteroBioLab), Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy. silvia.dei@unifi.it
Bellucci
Cristina
C
Buccioni
Michela
M
Ferraroni
Marta
M
Guandalini
Luca
L
Manetti
Dina
D
Marucci
Gabriella
G
Matucci
Rosanna
R
Nesi
Marta
M
Romanelli
Maria Novella
MN
Scapecchi
Serena
S
Teodori
Elisabetta
E
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D008024:Ligands; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D011976:Receptors, Muscarinic; D013454:Sulfoxides