Abstract
A new method for the preparation of N-benzylpyrrolomorphinans has been developed. Thus Michael reaction of the benzylimines of oxycodones and oxymorphones with nitrostyrenes gave a series of 4'-aryl-N-benzylpyrrolomorphinans. These were selective delta antagonists of much higher in vitro potency (with 5a having K(e) delta = <1 nM) than their binding affinities predicted. In mice in vivo assays 5a showed good delta antagonist activity in the anti-writhing analgesic assay and also inhibited delta agonist-induced convulsant activity.
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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CHO Cells
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Cricetinae
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Humans
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In Vitro Techniques
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Ligands
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Male
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Mice
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Morphinans / chemical synthesis*
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Morphinans / chemistry
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Morphinans / pharmacology
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Narcotic Antagonists / chemical synthesis*
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Narcotic Antagonists / chemistry
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Narcotic Antagonists / pharmacology
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Radioligand Assay
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / antagonists & inhibitors*
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Seizures / chemically induced
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Structure-Activity Relationship
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Transfection
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Vas Deferens / metabolism
Substances
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Ligands
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Morphinans
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Narcotic Antagonists
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Receptors, Opioid, delta