Abstract
Further modification of salvinorin A (1a), the major active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study that oxadiazole 11a and salvidivin A (12a), a photooxygenation product of 1a, have been identified as the first neoclerodane diterpenes with kappa antagonist activity. This indicates that additional structural modifications of 1a may lead to analogues with higher potency and utility as drug abuse medications.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Crystallography, X-Ray
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Diterpenes, Clerodane / chemical synthesis*
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Diterpenes, Clerodane / chemistry
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Diterpenes, Clerodane / pharmacology
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Furans / chemical synthesis*
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Furans / chemistry
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Furans / pharmacology
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Humans
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Molecular Structure
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Radioligand Assay
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, kappa / antagonists & inhibitors*
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / antagonists & inhibitors
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Salvia / chemistry*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Diterpenes, Clerodane
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Furans
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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salvinicin A
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salvinicin B