Abstract
The C(3)-substituent in morphinan opioids is of critical importance; the 3-OH group is usually associated with very much higher affinity for mu-receptors than H or -OMe. However in this series of 14beta-cinnamoylamino derivatives the codeinones (e.g. methoclocinnamox, MC-CAM) had unexpectedly high mu-opioid receptor affinity, similar to that of the morphinone (clocinnamox, C-CAM). The current report relates to the synthesis and in vitro evaluation of deoxyclocinnamox (DOC-CAM) which acted as a high-affinity opioid antagonist similar to C-CAM but with greater mu selectivity. Thus it appears that the C(3)-substituent does not play a major role in the binding of the 14beta-cinnamoyl series and that the cinnamoyl group itself may in fact be the dominant binding feature.
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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Binding, Competitive
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Brain / metabolism
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Cloning, Molecular
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Haplorhini
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Humans
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In Vitro Techniques
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Morphine Derivatives / chemical synthesis*
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Morphine Derivatives / chemistry
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Morphine Derivatives / metabolism
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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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Radioligand Assay
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Rats
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / antagonists & inhibitors*
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Receptors, Opioid, mu / metabolism
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Tumor Cells, Cultured
Substances
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3-deoxyclocinnamox
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Morphine Derivatives
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Narcotic Antagonists
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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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Guanosine 5'-O-(3-Thiotriphosphate)