Abstract
Sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Starting from a screening hit 8 that had modest affinity for the cannabinoid CB(2) receptor, a parallel synthesis approach and initial SAR are described, leading to compound 27 with 120-fold functional selectivity for the CB(2) receptor. This compound produced robust antiallodynic activity in rodent models of postoperative pain and neuropathic pain without traditional cannabinergic side effects.
MeSH terms
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Animals
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Benzamides / chemical synthesis
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Benzamides / pharmacology
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Benzamides / therapeutic use*
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Binding Sites
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Dose-Response Relationship, Drug
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Ligands
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Mice
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Models, Animal
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Models, Chemical
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Neuralgia / drug therapy*
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Pain Measurement / drug effects
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Rats
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Receptor, Cannabinoid, CB2 / chemistry
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Receptor, Cannabinoid, CB2 / metabolism*
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use*
Substances
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Benzamides
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Ligands
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Receptor, Cannabinoid, CB2
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Sulfonamides