(Z)-2-(N-acetylindol-3-ylmethylene)quinuclidin-3-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: (Z)-2-(N-acetylindol-3-ylmethylene)quinuclidin-3-one
• 英文别名: (2Z)-2-[(1-acetylindol-3-yl)methylidene]-1-azabicyclo[2.2.2]octan-3-one
• 化学式: C₁₈H₁₈N₂O₂
• 分子量: 294.353
• InChiKey: AYOODTCAGXPOPY-YVLHZVERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-2-(N-acetylindol-3-ylmethylene)quinuclidin-3-one 在 sodium hydroxide 作用下， 反应 0.5h， 生成 (Z)-2-(1H-indol-3-ylmethylene)quinuclidin-3-one
  参考文献：
  名称：

  (Z)-2-(1H-Indol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-one

  摘要：

  The title compound, C16H16N2O, which contains a double bond connecting an azabicyclic ring system to an indol-3-yl-methylene group, crystallizes from a solution in ethyl acetate. The geometries of the two crystallographically independent molecules are nearly identical. The crystal packing of the title compound involves two types of intermolecular hydrogen bond.

  DOI：

  10.1107/s0108270103026076
• 作为产物：
  描述：

  3-吲哚甲醛 在 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (Z)-2-(N-acetylindol-3-ylmethylene)quinuclidin-3-one
  参考文献：
  名称：

  Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel, high affinity ligands for CB1 and CB2 cannabinoid receptors

  摘要：

  A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R-2 = H, R-1 = F) and 13 (R = COOCH3, R-1 = R-2 = H) exhibited high affinity for CB2 receptors with K-i values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CBI receptor (K-i values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.025

文献信息

• (<i>Z</i>)-2-(1<i>H</i>-Indol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-one
  作者：Vijayakumar N. Sonar、Sean Parkin、Peter A. Crooks

  DOI：10.1107/s0108270103026076

  日期：2004.1.15

  The title compound, C16H16N2O, which contains a double bond connecting an azabicyclic ring system to an indol-3-yl-methylene group, crystallizes from a solution in ethyl acetate. The geometries of the two crystallographically independent molecules are nearly identical. The crystal packing of the title compound involves two types of intermolecular hydrogen bond.
• Novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents
  作者：Vijayakumar N. Sonar、Y. Thirupathi Reddy、Konjeti R. Sekhar、Soumya Sasi、Michael L. Freeman、Peter A. Crooks

  DOI：10.1016/j.bmcl.2007.10.035

  日期：2007.12

  Use of ionizing radiation is essential for the management of many human cancers, and therapeutic hyperthermia has been identified as a potent radio sensitizer. Radiation therapy combined with adjuvant hyperthermia represents a potential too] to provide outstanding local-regional control for refractory disease. (Z)-(+/-)-2-(N-Benzylindol-3-ylmethylene)quinuclidin-3-oI (2) and (Z)-(+/-)-2-(N-benzenesulfonylindol-3-ylmethylene)quinuclidin-3-ol (4) were initially identified as potent thermal sensitizers that could lower the threshold needed for thermal sensitivity to radiation treatment. To define the structural requirements of the molecule that are essential for thermal sensitization, we have synthesized and evaluated a series of (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one (9), and (Z)-()-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-oI (10) analogs that incorporate a variety of substituents in both the indole and N-benzyl moieties. These systematic structure-activity relationship (SAR) studies were designed to further the development and optimization of potential clinically useful thermal sensitizing agents. The most potent analog was compound 10 (R-1 = H, R 2 = 4-Cl), which potently inhibited (93% inhibition at 50 mu M) the growth of HT-29 cells after a 41 degrees C/2 h exposure. (c) 2007 Elsevier Ltd. All rights reserved.
• Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel, high affinity ligands for CB1 and CB2 cannabinoid receptors
  作者：Nikhil Reddy Madadi、Narsimha Reddy Penthala、Lisa K. Brents、Benjamin M. Ford、Paul L. Prather、Peter A. Crooks

  DOI：10.1016/j.bmcl.2013.02.025

  日期：2013.4

  A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R-2 = H, R-1 = F) and 13 (R = COOCH3, R-1 = R-2 = H) exhibited high affinity for CB2 receptors with K-i values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CBI receptor (K-i values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer. (C) 2013 Elsevier Ltd. All rights reserved.