Abstract
Novel tropane derivatives were characterized as muscarinic acetylcholine receptor antagonists (mAChRs). Through optimization of the structure-activity relationship around the tropane scaffold, the quaternary ammonium salt 34 was identified as a very potent M(3) mAChR antagonist. The compound was functionally active and displayed greater than 24 h duration of action in a mouse model of bronchoconstriction.
MeSH terms
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Animals
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Biological Availability
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Bronchi / drug effects
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Bronchi / physiology
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Bronchoconstriction / drug effects
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CHO Cells
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Calcium / metabolism
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Cricetinae
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Cricetulus
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Drug Design
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Humans
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In Vitro Techniques
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Mice
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Mice, Inbred BALB C
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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
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Radioligand Assay
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Rats
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Receptor, Muscarinic M1 / physiology
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Receptor, Muscarinic M2 / physiology
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Receptor, Muscarinic M3 / physiology
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Stereoisomerism
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Structure-Activity Relationship
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Tropanes / chemical synthesis*
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Tropanes / chemistry
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Tropanes / pharmacology
Substances
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(3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo( 3.2.1)octane bromide
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Biphenyl Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Muscarinic Antagonists
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Receptor, Muscarinic M1
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Receptor, Muscarinic M2
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Receptor, Muscarinic M3
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Tropanes
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Calcium