5-methyl-2-oxo-5-((trimethylsilyl)ethynyl)cyclohexanecarbonitrile | 1207110-51-7

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 5-methyl-2-oxo-5-((trimethylsilyl)ethynyl)cyclohexanecarbonitrile
• 英文别名: 5-methyl-2-oxo-5-(2-trimethylsilylethynyl)cyclohexane-1-carbonitrile
• CAS: 1207110-51-7
• 化学式: C₁₃H₁₉NOSi
• 分子量: 233.385
• InChiKey: QBCOUUCSWGVCEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 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：

  5-methyl-2-oxo-5-((trimethylsilyl)ethynyl)cyclohexanecarbonitrile 在 四丁基氟化铵 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 0.5h， 生成 3-ethynyl-3-methyl-6-oxocyclohex-1-enecarbonitrile
  参考文献：
  名称：

  Synthesis, Chemical Reactivity as Michael Acceptors, and Biological Potency of Monocyclic Cyanoenones, Novel and Highly Potent Anti-inflammatory and Cytoprotective Agents

  摘要：

  Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.

  DOI：

  10.1021/jm3003922
• 作为产物：
  描述：

  8-甲基-1,4-二噁螺[4,5]癸烷-8-羧酸乙酯 在 吡啶 、 chromium(VI) oxide 、 盐酸 、 六甲基磷酰三胺 、 lithium aluminium tetrahydride 、 正丁基锂 、 水 、 甲基锂 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 正庚烷 、 二氯甲烷 、 乙基苯 、 丙酮 为溶剂， 反应 9.41h， 生成 5-methyl-2-oxo-5-((trimethylsilyl)ethynyl)cyclohexanecarbonitrile
  参考文献：
  名称：

  Synthesis, Chemical Reactivity as Michael Acceptors, and Biological Potency of Monocyclic Cyanoenones, Novel and Highly Potent Anti-inflammatory and Cytoprotective Agents

  摘要：

  Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.

  DOI：

  10.1021/jm3003922

文献信息

• [EN] MONOCYCLIC CYANOENONES AND METHODS OF USE THEREOF<br/>[FR] CYANOÉNONES MONOCYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：DARTMOUTH COLLEGE

  公开号：WO2010011782A1

  公开（公告）日：2010-01-28

  The present invention features monocyclic cyanoenone compositions and methods for using the same in the treatment of diseases such as cancer, inflammatory diseases and neurodegenerative diseases.

  本发明涉及单环氰基烯酮组合物及其在治疗癌症、炎症性疾病和神经退行性疾病等疾病中的应用方法。
• MONOCYCLIC CYANOENONES AND METHODS OF USE THEREOF
  申请人：Honda Tadashi

  公开号：US20110196007A1

  公开（公告）日：2011-08-11

  The present invention features monocyclic cyanoenone compositions and methods for using the same in the treatment of diseases such as cancer, inflammatory diseases and neurodegenerative diseases.

  本发明涉及单环氰基烯酮组合物及其在治疗癌症、炎症性疾病和神经退行性疾病等疾病中的应用方法。
• Monocyclic cyanoenones and methods of use thereof
  申请人：Trustess of Dartmouth College

  公开号：US08314137B2

  公开（公告）日：2012-11-20

  The present invention features monocyclic cyanoenone compositions and methods for using the same in the treatment of diseases such as cancer, inflammatory diseases and neurodegenerative diseases.

  本发明涉及一种单环腈酮化合物及其在治疗癌症、炎症性疾病和神经退行性疾病等疾病中的使用方法。
• Synthesis, Chemical Reactivity as Michael Acceptors, and Biological Potency of Monocyclic Cyanoenones, Novel and Highly Potent Anti-inflammatory and Cytoprotective Agents
  作者：Suqing Zheng、Y. R. Santosh Laxmi、Emilie David、Albena T. Dinkova-Kostova、Katherine H. Shiavoni、Yanqing Ren、Ying Zheng、Isaac Trevino、Ronald Bumeister、Iwao Ojima、W. Christian Wigley、James B. Bliska、Dale F. Mierke、Tadashi Honda

  DOI：10.1021/jm3003922

  日期：2012.5.24

  Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.