Abstract
A novel class of cannabinoid-1 (CB1) receptor antagonists for the treatment of obesity is presented. The carboxamide linker in a set of 5,6-diaryl-pyrazine-2-amide derivatives was transformed into the corresponding thioamide, by using a one-pot synthesis. The structural series of thioamides not only showed retained CB1 potency (below 10nM), but also showed improved solubility. In addition, the neutral antagonist 2c significantly reduced body weight in cafeteria diet obese mice.
Copyright 2009 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Anti-Obesity Agents / chemical synthesis
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Anti-Obesity Agents / chemistry*
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Anti-Obesity Agents / pharmacokinetics
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Disease Models, Animal
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Mice
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Mice, Obese
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Obesity / drug therapy
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Pyrazines / chemistry*
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Pyrazines / pharmacokinetics
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
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Receptor, Cannabinoid, CB1 / metabolism
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Structure-Activity Relationship
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Thioamides / chemical synthesis
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Thioamides / chemistry*
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Thioamides / pharmacokinetics
Substances
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Anti-Obesity Agents
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Pyrazines
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Receptor, Cannabinoid, CB1
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Thioamides