1-((4S,5S)-2,2-Dimethyl-4-phenyl-[1,3]dioxan-5-yl)-3-(2-trifluoromethyl-phenyl)-urea

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-((4S,5S)-2,2-Dimethyl-4-phenyl-[1,3]dioxan-5-yl)-3-(2-trifluoromethyl-phenyl)-urea
• 英文别名: 1-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]-3-[2-(trifluoromethyl)phenyl]urea
• 化学式: C₂₀H₂₁F₃N₂O₃
• 分子量: 394.394
• InChiKey: AXUALTRIFFIKTO-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (4S,5S)-2,2-二甲基-4-苯基-1,3-二恶烷-5-胺 、 2-(三氟甲基)苯基异氰酸酯 以 正戊烷 为溶剂， 反应 2.0h， 生成 1-((4S,5S)-2,2-Dimethyl-4-phenyl-[1,3]dioxan-5-yl)-3-(2-trifluoromethyl-phenyl)-urea
  参考文献：
  名称：

  Novel substituted 4-phenyl-[1,3]dioxanes: potent and selective orexin receptor 2 (OX2R) antagonists

  摘要：

  Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A and B) interacting with two known G-protein coupled receptors (OX1R and OX2R). In addition to other biological functions, the orexin-2 receptor is thought to be an important modulator of sleep and wakefulness. Herein we describe a series of novel, selective OX2R antagonists consisting of substituted 4-phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3-((4S,5s)-2,2-dimethyl-4-phenyl[1,3]dioxan-5-yl)-urea, which is bound by the OX2R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the OX2R over the OX1R. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.032

文献信息

• [EN] SUBSTITUTED 4-PHENYL-[1,3]-DIOXANES<br/>[FR] 4-PHENYL-[1,3]-DIOXANES SUBSTITUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004052876A1

  公开（公告）日：2004-06-24

  Urea-containing, substituted 4-phenyl-[1,3]-dioxanes, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, obesity or a sleep/wake disorder mediated by orexin-2 are described.

  本文描述了含尿素、取代的4-苯基-[1,3]-二氧杂环戊烷类化合物的制备方法、含有这些化合物的组合物，以及利用它们治疗肥胖或由促觉醒素-2介导的睡眠/清醒障碍的方法。
• Substituted 4-phenyl-[1,3]-dioxanes
  申请人：——

  公开号：US20040147593A1

  公开（公告）日：2004-07-29

  Urea-containing, substituted 4-phenyl-[1,3]-dioxanes, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, obesity or a sleep/wake disorder mediated by orexin-2 are described.

  描述了含脲、取代的 4-苯基-[1,3]-二氧杂环戊烷、制造它们的方法、含有它们的组合物以及使用它们治疗肥胖症或由奥曲肽-2 介导的睡眠/觉醒障碍等疾病的方法。
• US6951882B2
  申请人：——

  公开号：US6951882B2

  公开（公告）日：2005-10-04
• Novel substituted 4-phenyl-[1,3]dioxanes: potent and selective orexin receptor 2 (OX2R) antagonists
  作者：Laura C McAtee、Steven W Sutton、Dale A Rudolph、Xiaobing Li、Leah E Aluisio、Victor K Phuong、Curt A Dvorak、Timothy W Lovenberg、Nicholas I Carruthers、Todd K Jones

  DOI：10.1016/j.bmcl.2004.06.032

  日期：2004.8

  Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A and B) interacting with two known G-protein coupled receptors (OX1R and OX2R). In addition to other biological functions, the orexin-2 receptor is thought to be an important modulator of sleep and wakefulness. Herein we describe a series of novel, selective OX2R antagonists consisting of substituted 4-phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3-((4S,5s)-2,2-dimethyl-4-phenyl[1,3]dioxan-5-yl)-urea, which is bound by the OX2R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the OX2R over the OX1R. (C) 2004 Elsevier Ltd. All rights reserved.