Abstract
SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacokinetics
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Amides / pharmacology
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Analgesics / chemical synthesis*
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Analgesics / pharmacokinetics
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Analgesics / pharmacology
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Animals
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Biological Availability
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Humans
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Hyperalgesia / drug therapy*
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Hyperalgesia / metabolism
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Neuralgia / drug therapy*
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Neuralgia / metabolism
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptor, Cannabinoid, CB1 / metabolism
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Receptor, Cannabinoid, CB2 / agonists*
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Receptor, Cannabinoid, CB2 / metabolism
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Structure-Activity Relationship
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Thiophenes / chemical synthesis*
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Thiophenes / pharmacokinetics
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Thiophenes / pharmacology
Substances
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Amides
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Analgesics
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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Thiophenes