Abstract
Methylation of the carbon atom C of compound 1, a potent and not selective muscarinic antagonist, was carried out. The resulting diastereomers were separated and the corresponding racemate further resolved to give four enantiomers, which were tested both as hydrogen oxalate and methiodide salts. The pharmacological results obtained at M1, M2 and M3 muscarinic receptor subtypes, show that methylation at C1, depending on the stereochemistry, increases antagonist potency, having thus the same effect of nitrogen quaternization. These results may well lead to the development of new potent antimuscarinic drugs lacking a cationic head.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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Dioxolanes / chemical synthesis
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Dioxolanes / chemistry
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Dioxolanes / pharmacology*
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Guinea Pigs
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Hydrocarbons, Iodinated / chemistry
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Hydrocarbons, Iodinated / pharmacology
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Ileum / chemistry
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Male
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Methylation
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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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Myocardium / chemistry
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Oxalates / chemistry
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Oxalates / pharmacology
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Protein Binding / drug effects
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Rabbits
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Receptors, Muscarinic / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Vas Deferens / chemistry
Substances
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(1-(2,2-diphenyl-(1,3)dioxolan-4-yl)-ethyl)-dimethyl-amine
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Dioxolanes
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Hydrocarbons, Iodinated
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Muscarinic Antagonists
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Oxalates
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Receptors, Muscarinic
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methyl iodide