Abstract
Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand moiety led to the identification of a number of potent derivatives.
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 / pharmacology
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CHO Cells
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Cricetinae
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Cricetulus
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Drug Discovery
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Humans
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Mice
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Microsomes, Liver / metabolism
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / pharmacology
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Receptors, Somatostatin / antagonists & inhibitors*
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Receptors, Somatostatin / metabolism
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Anti-Obesity Agents
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MCHR1 protein, human
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Pyridones
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Receptors, Somatostatin
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Recombinant Proteins