Abstract
A potent and selective antagonist of the melanocortin-4 receptor, 1-[2-[(1S)-(3-dimethylaminopropionyl)amino-2-methylpropyl]-6-methylphenyl]-4-[(2R)-methyl-3-(4-chlorophenyl)propionyl]piperazine (10d), was identified from a series piperazinebenzylamine attached with a N,N-dimethyl-beta-alanine side chain. This compound possessed high water solubility and exhibited good metabolic profiles. In animals, 10d showed moderate to good oral bioavailability and promoted food intake in tumor-bearing mice after oral administration.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Cachexia / drug therapy*
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Cachexia / etiology
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Cyclic AMP / metabolism
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Dogs
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Eating / drug effects
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Humans
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Macaca mulatta
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Male
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Mice
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Mice, Inbred C57BL
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Microsomes, Liver / metabolism
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Neoplasm Transplantation
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Neoplasms, Experimental / complications
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Piperazines / chemical synthesis*
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Piperazines / pharmacokinetics
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Piperazines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptor, Melanocortin, Type 4 / antagonists & inhibitors*
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Solubility
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Stereoisomerism
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Structure-Activity Relationship
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beta-Alanine / analogs & derivatives*
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beta-Alanine / chemical synthesis
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beta-Alanine / pharmacokinetics
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beta-Alanine / pharmacology
Substances
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1-(2-(1-(3-dimethylaminopropionyl)amino-2-methylpropyl)-4-methylphenyl)-4-(2-methyl-3-(4-chlorophenyl)propionyl)piperazine
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Piperazines
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Receptor, Melanocortin, Type 4
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beta-Alanine
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Cyclic AMP