Abstract
Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a mu agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for mu agonist activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding, Competitive / drug effects
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Diterpenes / chemical synthesis*
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Diterpenes / chemistry
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Diterpenes / pharmacology
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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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Drug Evaluation, Preclinical
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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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Pyrones / chemical synthesis*
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Pyrones / chemistry
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Pyrones / pharmacology
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / antagonists & inhibitors*
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Receptors, Opioid, mu / genetics
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Recombinant Proteins / agonists
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Salvia / chemistry*
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Structure-Activity Relationship
Substances
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9-(benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho(2,1-c)pyran-7-carboxylic acid methyl ester
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Diterpenes
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Diterpenes, Clerodane
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Furans
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Pyrones
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Receptors, Opioid, mu
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Recombinant Proteins
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neoclerodane
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salvinorin A