Enantioselectivity of muscarinic antagonists. 2,2-Dicyclohexyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodides and related 3-oxides.
The enantiomers of three chiral muscarinic antagonists carrying a 1,3-oxathiolane nucleus were prepared and their absolute configuration established. The enantioselectivity and tissue selectivity of such compounds were studied on rat bladder and guinea pig ileum and heart. The results show that introduction of a sulfoxide function brings about a small but definite enantioselectivity in the 1,3-oxathiolane compound (2), which in itself does not show enantioselectivity among the tissues studied. The results obtained point to differences among cardiac and ileal muscarinic receptors. Comparison of the absolute configuration related agonists shows that the most potent isomers of both series share the same absolute stereochemistry.
Romanelli
M N
MN
Dipartimento di Scienze Farmaceutiche, Firenze, Italy.
Teodori
E
E
Gualtieri
F
F
Angeli
P
P
Brasili
L
L
D000818:Animals; D016275:Atrial Function; D002217:Carbachol / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D007082:Ileum / Q000502:physiology; D008968:Molecular Conformation; D009116:Muscarine / Q000037:antagonists & inhibitors*; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes; D001743:Urinary Bladder / Q000502:physiology
D003510:Cyclohexanes; D006571:Heterocyclic Compounds; D011976:Receptors, Muscarinic; D013876:Thiophenes; C056976:2,2-dicyclohexyl-5-((dimethylamino)methyl)-1,3-oxathiolane methiodide; D009116:Muscarine; D002217:Carbachol