Abstract
The development of novel agents for the differentiation of neuronal nicotinic acetylcholine receptors (nAChRs) is important for the treatment of a variety of pathological conditions. We have prepared and evaluated a number of simpler analogues of the norditerpeniod alkaloid methyllycaconitine (MLA) in an effort to understand molecular determinants of nAChR*small molecule interactions. We have previously reported the synthesis and evaluation of a series of ring E analogues of MLA. We report here the optimization of the alpha3beta4* functional activity of this series of compounds through modification of the ester.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aconitine / analogs & derivatives*
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Aconitine / chemical synthesis*
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Aconitine / pharmacology
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Alkaloids / chemical synthesis
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Alkaloids / pharmacology
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Animals
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Binding, Competitive / drug effects
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Binding, Competitive / physiology
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Catecholamines / metabolism
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Cell Line
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Diterpenes / chemical synthesis
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Diterpenes / pharmacology
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Esters / chemistry
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Nicotinic Antagonists / chemical synthesis*
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Nicotinic Antagonists / pharmacology
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Receptors, Nicotinic / drug effects*
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Receptors, Nicotinic / metabolism
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Structure-Activity Relationship
Substances
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Alkaloids
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Catecholamines
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Diterpenes
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Esters
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Nicotinic Antagonists
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Receptors, Nicotinic
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nicotinic receptor alpha3beta4
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methyllycaconitine
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Aconitine