Abstract
Unexpectedly high affinity for opioid receptors has been observed for a novel series of cyclazocine analogues where the prototypic 8-OH was replaced by a carboxamido group. For mu and kappa opioid receptors, the primary carboxamido derivative of cyclazocine ((+/-)-15) displayed high affinity (Ki=0.41 and 0.53 nM, respectively) nearly comparable to cyclazocine. A high enantiopreference ((2R,6R,11R)-) for binding was also observed. Compound (+/-)-15 also displayed potent antinociception activity in mice when administered icv.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amides / chemistry*
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Amides / metabolism
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Analgesics, Non-Narcotic / chemical synthesis
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Analgesics, Non-Narcotic / chemistry*
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Analgesics, Non-Narcotic / metabolism
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Analgesics, Non-Narcotic / pharmacology
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Animals
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Cyclazocine / chemistry*
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Cyclazocine / metabolism
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Mice
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Molecular Structure
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Narcotic Antagonists / chemical synthesis
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Narcotic Antagonists / chemistry*
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Narcotic Antagonists / metabolism
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Narcotic Antagonists / pharmacology
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Radioligand Assay
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Receptors, Opioid, kappa / metabolism*
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Receptors, Opioid, mu / metabolism*
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Structure-Activity Relationship
Substances
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Amides
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Analgesics, Non-Narcotic
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Narcotic Antagonists
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Cyclazocine