Abstract
We identified (5'S)-10'-fluoro-6'-methyl-5',6'-dihydro-3'H-spiro[cyclopropane-1,4'-[2,6]diaza[2,5]methano[2,6]benzodiazonin]-7'(1'H)-one, 22b (DS34942424) with a unique and original bicyclic skeleton. 22b showed an orally potent analgesic in the acetic acid-induced writhing test and formalin test in ddY mice without sedation. Moreover, 22b did not exhibit mu opioid receptor agonist activity.
Keywords:
Alkaloid; Analgesic; Conolidine; Non-opioid analgesics.
Copyright © 2020 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Analgesics, Opioid / chemistry*
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Analgesics, Opioid / metabolism
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Analgesics, Opioid / pharmacology
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Analgesics, Opioid / therapeutic use
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Animals
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Behavior, Animal / drug effects
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Disease Models, Animal
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Drug Evaluation, Preclinical
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Drug Stability
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Male
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Mice
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Microsomes, Liver / metabolism
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Pain / chemically induced
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Pain / drug therapy
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Pain / pathology
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Receptors, Opioid, mu / agonists*
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Receptors, Opioid, mu / metabolism
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Spiro Compounds / chemistry*
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Spiro Compounds / metabolism
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Spiro Compounds / pharmacology
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Spiro Compounds / therapeutic use
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Structure-Activity Relationship
Substances
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Analgesics, Opioid
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Receptors, Opioid, mu
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Spiro Compounds