Discovery of 1-{2-[(1S)-(3-Dimethylamino-propionyl)amino-2-methylpropyl]-4-methyl-henyl}-4-[(2R)-methyl-3-(4-chlorophenyl)-propionyl]piperazine as an Orally Active Antagonist of the Mela

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• 作者：Chen Chen ; Wanlong Jiang ; Fabio Tucci ; Joe A Tran ; Beth A. Fleck ; Sam R. Hoare ; Margaret Joppa ; Stacy Markison ; Jenny Wen ; Yang Sai ; Michael Johns ; Ajay Madan ; Takung Chen ; Caroline W. Chen ; Dragan Ma
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 1, 2007
• 年：2007
• 卷：50
• 期：22
• 页码：5249 - 5252
• 全文大小：67K
• 年卷期：v.50,no.22(November 1, 2007)
• ISSN：1520-4804

文摘

A potent and selective antagonist of the melanocortin-4receptor, 1-{2-[(1S)-(3-dimethylaminopropionyl)amino-2-methylpropyl]-6-methylphenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)propionyl]piperazine (10d), was identified from a series piperazinebenzylamineattached with a N,N-dimethyl--alanine side chain. This compoundpossessed high water solubility and exhibited good metabolic profiles.In animals, 10d showed moderate to good oral bioavailability andpromoted food intake in tumor-bearing mice after oral administration.