Abstract
Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid mu-agonist (Fentanyl) and NSAID (Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase (COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Analgesics, Opioid / chemical synthesis
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Analgesics, Opioid / chemistry*
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Analgesics, Opioid / pharmacology*
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Animals
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry*
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Cyclooxygenase Inhibitors / pharmacology*
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Guinea Pigs
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Ileum / drug effects
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Indenes / chemical synthesis
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Indenes / chemistry
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Indenes / pharmacology
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Indoleacetic Acids / chemical synthesis
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Indoleacetic Acids / chemistry*
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Indoleacetic Acids / pharmacology*
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Male
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Mice
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Molecular Structure
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Myenteric Plexus / drug effects
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Pain / drug therapy
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Prostaglandin-Endoperoxide Synthases / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid / agonists
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Receptors, Opioid / metabolism
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Receptors, Opioid, mu
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Vas Deferens / drug effects
Substances
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Analgesics, Opioid
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Cyclooxygenase Inhibitors
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Indenes
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Indoleacetic Acids
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Receptors, Opioid
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Receptors, Opioid, mu
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indene
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Prostaglandin-Endoperoxide Synthases