Abstract
A series of diazabicyclo[3.3.0]octane substituted pyridines and pyrazines was synthesized and characterized at the α4β2 neuronal nicotinic acetylcholine receptor (nAChR). The compounds were designed to mimic the profile of ABT-089, high affinity binding ligand for the α4β2 nAChR, with limited agonist activity. Carboxamide derivatives of 3-(diazabicyclo[3.3.0]octane)-substituted pyridines or 2-(diazabicyclo[3.3.0]octane)-substituted pyrazines were found to have the desired binding and activity profile. The structure-activity relationship of these compounds is presented.
MeSH terms
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Animals
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Brain / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Cell Line, Tumor
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Drug Partial Agonism
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HEK293 Cells
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Humans
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In Vitro Techniques
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Ligands
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Neurons / metabolism
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Nicotinic Agonists / chemical synthesis*
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Nicotinic Agonists / pharmacokinetics
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Nicotinic Agonists / pharmacology
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Pyrazines / chemical synthesis*
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Pyrazines / pharmacokinetics
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Pyrazines / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacokinetics
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Pyridines / pharmacology
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Pyrrolidines / chemistry
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Radioligand Assay
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Rats
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Receptors, Nicotinic / metabolism*
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Recombinant Proteins / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Ligands
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Nicotinic Agonists
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Pyrazines
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Pyridines
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Pyrrolidines
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Receptors, Nicotinic
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Recombinant Proteins
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nicotinic receptor alpha4beta2
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pozanicline