Synthesis and evaluation of a new series of Neuropeptide S receptor antagonists

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• 作者：Jeffrey Y. Melamed ; Amy E. Zartman ; Nathan R. Kett ; Anthony L. Gotter ; Victor N. Uebele ; Duane R. Reiss ; Cindra L. Condra ; Christine F ; ozzi ; Laura S. Lubbers ; Blake A. Rowe ; Georgia B. McGaughey ; Mart
• 关键词：uropeptide S receptor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 August 2010
• 年：2010
• 卷：20
• 期：15
• 页码：4700-4703
• 全文大小：703 K

文摘

Administration of Neuropeptide S (NPS) has been shown to produce arousal, that is, independent of novelty and to induce wakefulness by suppressing all stages of sleep, as demonstrated by EEG recordings in rat. Medicinal chemistry efforts have identified a quinolinone class of potent NPSR antagonists that readily cross the blood–brain barrier. We detail here optimization efforts resulting in the identification of a potent NPSR antagonist which dose-dependently and specifically inhibited ¹²⁵I-NPS binding in the CNS when administered to rats.