6-(3-cyanophenyl)bicyclo[4.1.0]heptan-3-one | 540787-79-9

• 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: 6-(3-cyanophenyl)bicyclo[4.1.0]heptan-3-one
• 英文别名: 3-(4-Oxo-1-bicyclo[4.1.0]heptanyl)benzonitrile
• CAS: 540787-79-9
• 化学式: C₁₄H₁₃NO
• 分子量: 211.263
• InChiKey: CTWBQTIGZQHKIW-UHFFFAOYSA-N

物化性质

• 沸点：
  369.8±42.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  6-(3-cyanophenyl)bicyclo[4.1.0]heptan-3-one 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Novel aminobenzimidazoles as selective MCH-R1 antagonists for the treatment of metabolic diseases

  摘要：

  A series of novel aminobenzimidazoles was prepared and evaluated for h-MCH-R1 antagonist properties. Most of the compounds showed excellent h-MCH-R1 binding affinity as well as mouse ex vivo binding. Compounds 9 and 18 were active in mouse DIO studies at 30 mpk. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.058
• 作为产物：
  描述：

  4-(3-cyanophenyl)-3-cyclohexen-1-one ethylene ketal 在 diethylzinc 、 三氟乙酸 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 6-(3-cyanophenyl)bicyclo[4.1.0]heptan-3-one
  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

• Aminobenzimidazoles as selective melanin concentrating hormone receptor antagonists for the treatment of obesity and related disorders
  申请人：Sasikumar K. Thavalakulamgara

  公开号：US20050085488A1

  公开（公告）日：2005-04-21

  The present invention discloses compounds of formula I wherein Ar, Z, m, n, p, R 1 and R 8 are herein defined, said compounds being novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

  本发明公开了化合物I的公式，其中Ar、Z、m、n、p、R1和R8如下定义，所述化合物是新型黑素浓缩激素（MCH）拮抗剂，以及制备这类化合物的方法。在另一实施方案中，该发明公开了包含这种MCH拮抗剂的药物组合物，以及使用它们治疗肥胖、代谢紊乱、食欲紊乱（如暴食症）和糖尿病的方法。
• 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。
• [EN] N-ARYL-N'-ARYLCYCLOALKYL-UREA DERIVATIVES AS MCH ANTAGONISTS FOR THE TREATMENT OF OBESITY<br/>[FR] DERIVES DU N-ARYL-N'-ARYLCYCLOALKYL-UREE, ANTAGONISTES DE L'HORMONE MCH, TRAITANT L'OBESITE
  申请人：SCHERING CORP

  公开号：WO2003047568A1

  公开（公告）日：2003-06-12

  The present invention discloses compounds of the formula I which, are novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

  本发明揭示了式I的化合物，它们是黑色素浓聚激素（MCH）的新型拮抗剂，以及制备这些化合物的方法。在另一实施例中，本发明揭示了包含这些MCH拮抗剂的药物组合物，以及使用它们治疗肥胖症、代谢紊乱、食欲紊乱（如暴食症）和糖尿病的方法。
• MCH antagonists for the treatment of obesity
  申请人：Schering Corporation

  公开号：US20040122017A1

  公开（公告）日：2004-06-24

  The present invention discloses compounds which, are novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

  本发明揭示了一些化合物，这些化合物是黑色素浓聚激素（MCH）的新型拮抗剂，并揭示了制备这些化合物的方法。在另一种实施方式中，本发明揭示了包含这些MCH拮抗剂的药物组合物，以及使用它们治疗肥胖、代谢紊乱、进食障碍如过度进食和糖尿病的方法。
• SAR study of bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor R1 antagonists: Taming hERG
  作者：Jing Su、Brian A. McKittrick、Haiqun Tang、Duane A. Burnett、John W. Clader、William J. Greenlee、Brian E. Hawes、Kim O’Neill、Brian Spar、Blair Weig、Timothy Kowalski、Steve Sorota、Cheng Li、Tongtong Liu

  DOI：10.1016/j.bmc.2007.05.068

  日期：2007.8

  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.