3-(4-oxo-bicyclo[3.1.0]hex-1-yl)benzonitrile

• 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-oxo-bicyclo[3.1.0]hex-1-yl)benzonitrile
• 英文别名: 3-[(1S,5S)-4-oxo-1-bicyclo[3.1.0]hexanyl]benzonitrile
• 化学式: C₁₃H₁₁NO
• 分子量: 197.236
• InChiKey: CNSIRYJADWIMDD-DGCLKSJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(4-oxo-bicyclo[3.1.0]hex-1-yl)benzonitrile 在 titanium(IV) isopropylate 、 四溴化碳 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 54.75h， 生成 3-{(1R,4S,5R)-4-[4-(4-Methyl-piperazin-1-yl)-butylamino]-bicyclo[3.1.0]hex-1-yl}-benzonitrile
  参考文献：
  名称：

  Discovery of Orally Efficacious Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Agents. Synthesis, SAR, and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas

  摘要：

  Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study.

  DOI：

  10.1021/jm050886n
• 作为产物：
  描述：

  3-(3-氧代-1-环戊基)-苯腈 在 吡啶 、 sodium tetrahydroborate 、 cerium(III) chloride 、 diethylzinc 、 戴斯-马丁氧化剂 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 69.0h， 生成 3-(4-oxo-bicyclo[3.1.0]hex-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

• 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。
• Discovery of Orally Efficacious Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Agents. Synthesis, SAR, and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas
  作者：Mark D. McBriar、Henry Guzik、Sherry Shapiro、Jaroslava Paruchova、Ruo Xu、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、Constance Farley、John Cook

  DOI：10.1021/jm050886n

  日期：2006.4.1

  Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study.