Abstract
In investigation of the effects of 14-substitution in the indolomorphinan series of delta-selective opioid ligands, 5,14-bridged indolomorphinans (4) were prepared from the equivalent dihydrothebainone acid-catalyzed rearrangement products of the dihydrothevinols. Though the new ligands generally had low affinity for opioid receptors and no delta-selectivity, 4b had high kappa-affinity and substantial selectivity which was also seen in the precursor morphinanone (3b). This indicates that the methylbenzylidene-substituted bridge in these compounds is a dominant kappa-opioid receptor binding motif.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bridged-Ring Compounds / chemical synthesis*
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Bridged-Ring Compounds / chemistry
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Bridged-Ring Compounds / pharmacology
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CHO Cells
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Cricetinae
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Ligands
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Morphinans / chemical synthesis*
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Morphinans / chemistry
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Morphinans / pharmacology
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Receptors, Opioid, delta / metabolism*
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Receptors, Opioid, kappa / metabolism*
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Receptors, Opioid, mu / metabolism
Substances
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Bridged-Ring Compounds
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Indoles
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Ligands
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Morphinans
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu