Abstract
6'-Methylpyrido[3,4-b]norhomotropane [synthesis as the racemate reported here] is more potent at the alpha4beta2 nicotinic receptor than any previous bridged nicotinoid. The two nitrogens and 6'-methyl substituent are superimposable on the two nitrogens and 6-chloro substituent of epibatidine, with the best fit on comparing the chair conformer of the (1R)-pyridonorhomotropane with natural (1R)-epibatidine. In this pharmacophore model, the 6'-methyl substituent may be equivalent to the acetyl methyl of acetylcholine.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Bridged Bicyclo Compounds, Heterocyclic
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Humans
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Models, Molecular
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Molecular Conformation
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Nicotine / analogs & derivatives
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Protein Binding
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Pyridines / chemical synthesis*
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Pyridines / chemistry*
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Pyridines / pharmacology
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Receptors, Nicotinic / chemistry*
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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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6'-methylpyrido(3,4-b)norhomotropane
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Bridged Bicyclo Compounds, Heterocyclic
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Pyridines
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Receptors, Nicotinic
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Tropanes
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nicotinic receptor alpha4beta2
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pyrido(3,4-b)norhomotropane
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Nicotine
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epibatidine