Abstract
Several derivatives with an azabicyclo[2.2.2]octane skeleton having a 7-amide side chain were synthesized. Compounds that had an electron-donating group exhibited high affinity for the μ opioid receptor while those with a bulky substituent at the 8-nitrogen atom had low affinities for all receptor types. High affinities and selectivities for the κ receptor resulted from the introduction of the longer amide side chain at the 7α-position. Our studies indicate that the orientation of the amide side chain at the 7-position within the azabicyclo[2.2.2]octane skeleton is related to selectivity for the κ receptor.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Analgesics, Opioid / chemical synthesis*
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Analgesics, Opioid / chemistry
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Azabicyclo Compounds / chemical synthesis*
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Azabicyclo Compounds / chemistry
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Biological Assay
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Drug Design
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Humans
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Ligands
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / chemistry*
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, kappa / chemistry*
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / chemistry*
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Sensitivity and Specificity
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Structure-Activity Relationship
Substances
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Amides
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Analgesics, Opioid
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Azabicyclo Compounds
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Ligands
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu