Abstract
Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia.
MeSH terms
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Animals
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Anti-Obesity Agents / chemical synthesis
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Anti-Obesity Agents / pharmacology
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Brain Chemistry
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Cannabinoid Receptor Modulators / chemical synthesis*
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Cannabinoid Receptor Modulators / pharmacology
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Humans
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Hypothermia / drug therapy
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Inhibitory Concentration 50
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Pharmacokinetics
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Rats
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / drug effects*
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology
Substances
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Anti-Obesity Agents
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Cannabinoid Receptor Modulators
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Receptor, Cannabinoid, CB1
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Sulfonamides