3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-bicyclo[4.1.0]hept-1-yl}-benzonitrile | 869708-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-bicyclo[4.1.0]hept-1-yl}-benzonitrile
• CAS: 869708-42-9
• 化学式: C₂₀H₂₇N₃O
• 分子量: 325.454
• InChiKey: NBCZMOFHQBDLJU-WMGUDHAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  59.29
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-溴苯基异氰酸酯 、 3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-bicyclo[4.1.0]hept-1-yl}-benzonitrile 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  SAR study of bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor R1 antagonists: Taming hERG

  摘要：

  To improve the ex vivo potency of MCH inhibitor la and to address its hERG liability, a structure-activity study was carried out, focusing on three regions of the lead structure. Introduction of new side chains with basic nitrogen improved in vitro and ex vivo bindings. Many potent compounds with K-i < 10 nM were discovered (compounds 6a-j) and several Compounds (14-17) had excellent ex vivo binding at 6 h and 24 h. Attenuating the basicity of nitrogen on the side chain, and in particular, introduction of a polar group such as aminomethyl on the distal phenyl ring significantly lowered the hERG activity. Further replacement of the distal phenyl group with heteroaryl groups in the cyclohexene series provided compounds such as 281 with excellent ex vivo activity with much reduced hERG liability. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.068
• 作为产物：
  描述：

  4-(3-cyanophenyl)-4-hydroxycyclohexan-1-one ethylene ketal 在 diethylzinc 、 三乙酰氧基硼氢化钠 、 甲基磺酰氯 、 三乙胺 、 三氟乙酸 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 19.5h， 生成 3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-bicyclo[4.1.0]hept-1-yl}-benzonitrile
  参考文献：
  名称：

  发现双环烷基尿素黑色素浓缩激素受体拮抗剂：口服有效的减肥药。

  摘要：

  黑色素浓缩激素（MCH）参与食物摄入和能量稳态的调节。MCH受体的拮抗剂有望影响食物摄入和体重增加，使MCH-R1成为肥胖治疗的诱人靶标。在本文中，我们报告了在啮齿类肥胖症模型中表现出体内功效的新型口服活性MCH-R1拮抗剂的发现。

  DOI：

  10.1021/jm049035q

文献信息

• Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists
  作者：Ruo Xu、Shengjian Li、Jaroslava Paruchova、Mark D. McBriar、Henry Guzik、Anandan Palani、John W. Clader、Kathleen Cox、William J. Greenlee、Brian E. Hawes、Timothy J. Kowalski、Kim O’Neill、Brian D. Spar、Blair Weig、Daniel J. Weston

  DOI：10.1016/j.bmc.2005.12.046

  日期：2006.5

  Melanin concentrating hormone (MCH) receptor antagonists have been proposed as potential treatments of obesity. MCH receptor antagonists with a biphenylamine subunit have been reported previously at Schering-Plough. Herein, we report the discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of the biphenylamine moiety, in order to eliminate its potential mutagenic liability. Structure-activity relationships in this series were found to be very similar to those of the original biphenylamine series, suggesting that the two series have similar binding modes. (c) 2006 Elsevier Ltd. All rights reserved.