Abstract
The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1-selective muscarinic agonist. Efficacy and m1 selectivity reside in the R enantiomer, (R)-24Z (CI-1017).
MeSH terms
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3T3 Cells
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Adenylyl Cyclase Inhibitors
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / toxicity
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CHO Cells
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Cricetinae
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Drug Design*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / toxicity
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Humans
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Inositol Phosphates / biosynthesis
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Male
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Memory / drug effects
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Mice
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Muscarinic Agonists / chemical synthesis*
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Muscarinic Agonists / metabolism
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Muscarinic Agonists / pharmacology
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Muscarinic Agonists / toxicity
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Oximes / chemical synthesis*
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Oximes / metabolism
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Oximes / pharmacology
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Oximes / toxicity
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Rats
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Receptor, Muscarinic M1
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Receptors, Muscarinic / drug effects*
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Receptors, Muscarinic / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Transfection
Substances
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Adenylyl Cyclase Inhibitors
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Bridged Bicyclo Compounds, Heterocyclic
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Enzyme Inhibitors
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Inositol Phosphates
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Muscarinic Agonists
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Oximes
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Receptor, Muscarinic M1
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Receptors, Muscarinic
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PD 142505-0028