Abstract
In a continued effort to find new substitution patterns in morphinans that would produce strong antinociception while inducing lesser side effects, 4,5-oxygen bridge-opened 6-cyano-substituted N-methylmorphinans (1-3) were synthesized. All compounds showed high affinities in the low nanomolar range to the mu opioid receptor and decreased interaction with delta and kappa receptors, thus being mu selective. When tested in vivo, the 6-cyanomorphinanas acted as potent antinociceptive agents which were either more active or equipotent to their 6-keto analogues 4-6.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / chemistry
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Analgesics / pharmacology
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Animals
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Brain / metabolism
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In Vitro Techniques
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Mice
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Mice, Inbred ICR
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Morphinans / chemical synthesis*
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Morphinans / chemistry
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Morphinans / pharmacology
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology
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Rats
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Receptors, Opioid / drug effects*
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Receptors, Opioid / metabolism
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Receptors, Opioid, delta / drug effects
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / drug effects
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / drug effects
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Receptors, Opioid, mu / metabolism
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Structure-Activity Relationship
Substances
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Analgesics
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Morphinans
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Nitriles
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Receptors, Opioid
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu