Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists

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• 作者：Takashi Nagahara ; Tsuyoshi Saitoh ; Noriki Kutsumura ; Yoko Irukayama-Tomobe ; Yasuhiro Ogawa ; Daisuke Kuroda ; Hiroaki Gouda ; Hidetoshi Kumagai ; Hideaki Fujii ; Masashi Yanagisawa ; Hiroshi Nagase
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：October 22, 2015
• 年：2015
• 卷：58
• 期：20
• 页码：7931-7937
• 全文大小：424K
• ISSN：1520-4804

文摘

Orexins are a family of neuropeptides that regulate sleep/wakefulness, acting on two G-protein-coupled receptors, orexin receptors 1 (OX1R) and 2 (OX2R). Genetic and pharmacologic evidence suggests that orexin receptor agonists, especially OX2R agonist, will be useful for mechanistic therapy of the sleep disorder narcolepsy/cataplexy. We herein report the discovery of a potent (EC₅₀ on OX2R is 0.023 渭M) and OX2R-selective (OX1R/OX2R EC₅₀ ratio is 70) agonist, 4鈥?methoxy-N,N-dimethyl-3鈥?[N-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl)sulfamoyl]-(1,1鈥?biphenyl)-3-carboxamide 26.