Abstract
The synthesis, structure-activity relationship (SAR) studies and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles are described. The target compounds 6-18 represent a novel class of potent and selective CB(1) receptor antagonists. Based on X-ray diffraction data, the orally active 17 is shown to elicit a different intramolecular H-bonding mode as compared to ibipinabant (3) and SLV330 (4).
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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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 / pharmacology
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Binding Sites
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Crystallography, X-Ray
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Humans
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Hydrogen Bonding
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Molecular Conformation
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Rats
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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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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Anti-Obesity Agents
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Pyrazoles
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Receptor, Cannabinoid, CB1
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Sulfonamides