Abstract
A series of pyrrolidinones derived from phenylalanines were synthesized as potent antagonists of the human melanocortin-4 receptor. These compounds showed high potencies and selectivities, and several of them had good oral bioavailabilities. In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Body Composition
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Body Weight
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Cachexia / drug therapy*
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Disease Models, Animal
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Structure
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Pyrrolidinones / administration & dosage
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Pyrrolidinones / chemistry*
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Pyrrolidinones / pharmacology*
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Pyrrolidinones / therapeutic use
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Receptor, Melanocortin, Type 4 / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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MC4R protein, human
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Pyrrolidinones
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Receptor, Melanocortin, Type 4