Abstract
A number of analogs of the natural product himbacine were synthesized employing variations at the heterocyclic unit and the tether that links the heterocyclic unit to the tricyclic motif. Several of these analogs had M(2) affinity and M(1)/M(2) selectivity comparable to those of himbacine. The structural and stereochemical requirements of the heterocyclic unit for muscarinic binding are discussed in the light of these data.
MeSH terms
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Alkaloids / chemistry
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Alkaloids / pharmacology*
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Cloning, Molecular
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Furans
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Heterocyclic Compounds / chemical synthesis
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Heterocyclic Compounds / pharmacology*
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Humans
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Molecular Structure
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Muscarinic Antagonists / chemical synthesis*
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Muscarinic Antagonists / pharmacology
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Naphthalenes
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Parasympatholytics / chemical synthesis*
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Parasympatholytics / pharmacology
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Piperidines
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Receptors, Muscarinic / drug effects
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Receptors, Muscarinic / physiology*
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Recombinant Proteins / antagonists & inhibitors
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Structure-Activity Relationship
Substances
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Alkaloids
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Furans
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Heterocyclic Compounds
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Muscarinic Antagonists
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Naphthalenes
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Parasympatholytics
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Piperidines
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Receptors, Muscarinic
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Recombinant Proteins
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himbacine