Abstract
The 14-aminodihydromorphinone and codeinone series of opioid ligands have produced a number of ligands of substantial interest. To investigate the importance of the 14-substituent, a series of analogues in which the side chain length is varied and the amide and alkene functions are reduced have been prepared. Binding affinity, particularly at the mu-opioid receptor (MOR), was largely determined by the aromatic group of the side chain. In the [35S]GTPgammaS functional assay, the ligands having a three-carbon side chain were more potent antagonists than their longer chain counterparts, while shorter, two-carbon chain analogues were of higher MOR efficacy, an effect that was confirmed in vivo. Wash-resistant binding was observed within this series and appeared to be unrelated to side-chain length.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amines / chemical synthesis*
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Amines / chemistry
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Amines / pharmacology
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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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Cell Line
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Cricetinae
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Ligands
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Mice
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Morphine Derivatives / chemical synthesis*
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Morphine Derivatives / chemistry
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Morphine Derivatives / pharmacology
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Narcotic Antagonists*
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Pain Measurement
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Radioligand Assay
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Receptors, Opioid / agonists*
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Receptors, Opioid / metabolism
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, kappa / antagonists & inhibitors
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Amines
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Analgesics
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Ligands
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Morphine Derivatives
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Narcotic Antagonists
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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
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Guanosine 5'-O-(3-Thiotriphosphate)