Abstract
A series of himbacine (1)-related analogues has been prepared featuring three different isomeric configurations with respect to the B-ring (a, b and natural c) and three different interconnecting two-carbon unsaturated units [natural (E)-ene, (Z)-ene, and yne]. The study of the binding affinities of the nine resulting compounds, including synthetic (+)-himbacine (3c), towards the M(1)-M(4) muscarine receptor subtypes revealed that analogues 3a and 5c display a promising 10-fold selectivity for the M(2) receptor as compared to the M(1) receptor.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemistry*
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Alkaloids / pharmacology*
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Animals
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Binding, Competitive
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CHO Cells / metabolism
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Cricetinae
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Furans
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Humans
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Muscarinic Antagonists / chemical synthesis*
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Muscarinic Antagonists / pharmacology*
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Naphthalenes
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Piperidines
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Protein Binding
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Receptors, Muscarinic / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Alkaloids
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Furans
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Muscarinic Antagonists
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Naphthalenes
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Piperidines
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Receptors, Muscarinic
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himbacine