Discovery of 1-{2-[(1S)-(3-Dimethylamino-propionyl)amino-2-methylpropyl]-4-methyl-phenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)-propionyl]piperazine as an Orally Active Antagonist of the Melanocortin-4 Receptor for the Potential Treatment of Cachexia

Autor:	Michael Johns, Beth A. Fleck, Ajay Madan, Dragan Marinkovic, Margaret Joppa, Chen Chen, Stacy Markison, Wanlong Jiang, Melissa Arellano, Alan C. Foster, Joe A. Tran, Fabio C. Tucci, Takung Chen, Jenny Wen, Yang Sai, Sam R. J. Hoare, Caroline W. Chen, John Saunders
Rok vydání:	2007
Předmět:	Male Cachexia Stereochemistry Administration Oral Biological Availability Chemical synthesis Piperazines Rats Sprague-Dawley Eating Mice Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Dogs Oral administration Drug Discovery Cyclic AMP Animals Humans Structure–activity relationship Chemistry Antagonist Stereoisomerism Neoplasms Experimental Macaca mulatta Rats Bioavailability Mice Inbred C57BL Melanocortin 4 receptor Piperazine Solubility Microsomes Liver beta-Alanine Receptor Melanocortin Type 4 Molecular Medicine Melanocortin Neoplasm Transplantation
Zdroj:	Journal of Medicinal Chemistry. 50:5249-5252
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
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