3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-cyclohexyl}-benzonitrile | 541528-03-4

• 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: 3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-cyclohexyl}-benzonitrile
• 英文别名: 3-[4-[2-[(3R)-3-hydroxypyrrolidin-1-yl]ethylamino]cyclohexyl]benzonitrile
• CAS: 541528-03-4
• 化学式: C₁₉H₂₇N₃O
• 分子量: 313.443
• InChiKey: HKSAOXVUIFUGQZ-NKELODKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  59.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-cyclohexyl}-benzonitrile 、 异氰酸- 4-氟-3-(三氟甲基)苯酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以36%的产率得到1-[4-(3-Cyano-phenyl)-cyclohexyl]-3-(4-fluoro-3-trifluoromethyl-phenyl)-1-[2-((R)-3-hydroxy-pyrrolidin-1-yl)-ethyl]-urea; hydrochloride
  参考文献：
  名称：

  Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2005.12.046
• 作为产物：
  描述：

  4-(3-cyanophenyl)-4-hydroxycyclohexan-1-one ethylene ketal 在 三乙酰氧基硼氢化钠 、 戴斯-马丁氧化剂 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 50.0 ℃ 、310.26 kPa 条件下， 反应 33.0h， 生成 3-{4-[2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethylamino]-cyclohexyl}-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

• Discovery of Bicycloalkyl Urea Melanin Concentrating Hormone Receptor Antagonists:  Orally Efficacious Antiobesity Therapeutics
  作者：Mark D. McBriar、Henry Guzik、Ruo Xu、Jaroslava Paruchova、Shengjian Li、Anandan Palani、John W. Clader、William J. Greenlee、Brian E. Hawes、Timothy J. Kowalski、Kim O'Neill、Brian Spar、Blair Weig

  DOI：10.1021/jm049035q

  日期：2005.4.1

  concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 antagonists that exhibit in vivo efficacy in rodent obesity models.

  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。
• 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.