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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Guinea Pigs
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Humans
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Ileum / drug effects
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Ileum / physiology
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In Vitro Techniques
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Male
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Muscarinic Antagonists / chemical synthesis*
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Muscarinic Antagonists / chemistry
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Muscarinic Antagonists / pharmacology
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Myocardial Contraction / drug effects
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology
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Rabbits
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Radioligand Assay
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Receptors, Muscarinic / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Thiophenes / chemical synthesis*
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Thiophenes / chemistry
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Thiophenes / pharmacology
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Vas Deferens / drug effects
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Vas Deferens / physiology
Substances
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Muscarinic Antagonists
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Pyrrolidines
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Receptors, Muscarinic
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Thiophenes