Abstract
In an effort to probe the steric influence of C5 substitution of the pyridine ring on CNS binding affinity, analogues of 1 substituted with a bulky moiety--such as phenyl, substituted phenyl, or heteroaryl-were synthesized and tested in vitro for neuronal nicotinic acetylcholine receptor binding affinity. The substituted analogues exhibited Ki values ranging from 0.055 to 0.69 nM compared to a Ki value of 0.15 nM for compound 1. Assessment of functional activity at subtypes of neuronal nicotinic acetylcholine receptors led to identify several agonists and antagonists.
MeSH terms
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Cell Line
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Humans
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Ligands
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Molecular Structure
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Nicotinic Agonists / chemical synthesis
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Nicotinic Agonists / chemistry*
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Nicotinic Agonists / metabolism
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Nicotinic Agonists / pharmacology
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Nicotinic Antagonists / chemical synthesis
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Nicotinic Antagonists / chemistry*
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Nicotinic Antagonists / metabolism
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Nicotinic Antagonists / pharmacology
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Protein Binding
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / metabolism
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Pyridines / pharmacology
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Pyrrolidines / chemical synthesis
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Pyrrolidines / chemistry*
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Pyrrolidines / metabolism
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Pyrrolidines / pharmacology
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Receptors, Nicotinic / chemistry
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Receptors, Nicotinic / metabolism*
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Structure-Activity Relationship
Substances
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3-(2-(pyrrolidinyl)methoxy)pyridine
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Ligands
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Nicotinic Agonists
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Nicotinic Antagonists
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Pyridines
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Pyrrolidines
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Receptors, Nicotinic