N-propargyltetrahydro-γ-carboline | 1147893-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-propargyltetrahydro-γ-carboline
• 英文别名: 2,8-dimethyl-5-(prop-2-ynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole；2,3,4,5-tetrahydro-2,8-dimethyl-5-(prop-2-ynyl)-1H-pyrido[4,3-b]indole；2,8-dimethyl-5-prop-2-ynyl-3,4-dihydro-1H-pyrido[4,3-b]indole
• CAS: 1147893-57-9
• 化学式: C₁₆H₁₈N₂
• 分子量: 238.332
• InChiKey: DPZLBQHQZFUJNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 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：
  8.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-propargyltetrahydro-γ-carboline 、 1,4-二叠氮基丁烷 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 以81%的产率得到1,2-bis(4-{[2,8-dimethyl-3,4-dihydro-1H-pyrido-[4,3-b]indol-5(2H)-yl]methyl}-1H-1,2,3-triazol-1-yl)-butane
  参考文献：
  名称：

  Copper-catalyzed 1,3-Dipolar Cycloaddition of Substituted N-Propargylindoles and Terminal Diazidoalkanes

  摘要：

  Copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition was studied of substituted N-propargylindoles and diazidoalkanes leading to symmetric conjugates of substituted indoles with bistriazole-containing spacer.

  DOI：

  10.1134/s1070363218060361
• 作为产物：
  描述：

  3-溴丙炔 、 2,8-二甲基-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 在 potassium tert-butylate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.25h， 以60.6%的产率得到N-propargyltetrahydro-γ-carboline
  参考文献：
  名称：

  Furoxans (1,2,5-Oxadiazole-N-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents

  摘要：

  Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to the furoxan ring system led to modulation of reactivity toward bioactivation, studied by HPLC-MS/MS analysis of reaction products. Attenuated reactivity unmasked the cytoprotective actions of NO in contrast to the cytotoxic actions of higher NO fluxes reported previously for furoxans. Neuroprotection was observed in primary neuronal cell cultures following oxygen glucose deprivation (OGD). Neuroprotective activity was observed to correlate with thiol-dependent bioactivation to produce NO2-, but not with depletion of free thiol itself. Neuroprotection was abrogated upon cotreatment with a sGC inhibitor, ODQ, thus supporting activation of the NO/sGC/CREB signaling cascade by furoxans. Long-term potentiation (LTP), essential for learning and memory, has been shown to be potentiated by NO signaling, therefore, a peptidomimetic furoxan was tested in hippocampal slices treated with oligomeric amyloid-beta peptide (A beta) and was shown to restore synaptic function. The novel observation of furoxan activity of potential therapeutic use in the CNS warrants further studies.

  DOI：

  10.1021/jm201504s

文献信息

• [EN] PYRIDO (4,3-B) INDOLES CONTAINING RIGID MOIETIES<br/>[FR] PYRIDO[4,3-B]INDOLES CONTENANT DES FRAGMENTS RIGIDES
  申请人：MEDIVATION TECHNOLOGIES INC

  公开号：WO2010051501A1

  公开（公告）日：2010-05-06

  This disclosure is directed to pyrido[4,3-b]indoles having rigid moieties. The compounds in one embodiment are pyrido[4,3-b]indoles having an unsaturated hydrocarbon moiety. The compounds in another embodiment are pyrido[4,3-b]indoles having a cycloalkyl, cycloalkenyl or heterocyclyl moiety. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

  本公开涉及具有刚性基团的吡啶并[4,3-b]吲哚化合物。在一个实施例中，这些化合物是具有不饱和碳氢基团的吡啶并[4,3-b]吲哚化合物。在另一个实施例中，这些化合物是具有环烷基、环烯基或杂环基团的吡啶并[4,3-b]吲哚化合物。还提供了包括这些化合物的药物组合物，以及使用这些化合物在各种治疗应用中的方法，包括治疗认知障碍、精神障碍、神经递质介导的障碍和/或神经元障碍。
• [EN] NEW TETRACYCLIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS TÉTRACYCLIQUES
  申请人：MEDIVATION TECHNOLOGIES INC

  公开号：WO2009055828A1

  公开（公告）日：2009-04-30

  This disclosure relates to new tetracyclic compounds that may be used to modulate a histamine receptor in an individual. The compounds in one embodiment are tetracyclic [4,3- b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

  这项披露涉及可能用于调节个体组织胺受体的新四环化合物。在一个实施例中，这些化合物是四环[4,3- b]吲哚类化合物。此外还提供了包含这些化合物的药物组合物，以及使用这些化合物进行各种治疗应用的方法，包括治疗认知障碍、精神障碍、神经递质介导的障碍和/或神经元障碍。
• N-Propargyltetrahydrocarbazoles and N-propargyltetrahydro-γ-carbolines in 1,3-cycloaddition with azide-containing pharmacophores
  作者：V. B. Sokolov、A. Yu. Aksinenko、T. A. Epishina、T. V. Goreva

  DOI：10.1007/s11172-019-2571-7

  日期：2019.7

  A modification of tetrahydrocarbazoles and tetrahydro-γ-carbolines with pharmacophore ligands was performed based on the copper-catalyzed 1,3-dipolar cycloaddition of their N-propargyl derivatives to azide-containing carbazoles, tetrahydrocarbazoles, 1-aminoadamantanes, and phenothiazine.

  在铜催化下，四氢咔唑和四氢-γ-咔啉的 N-丙炔基衍生物与含叠氮化物的咔唑、四氢咔唑、1-氨基金刚烷和吩噻嗪发生了 1,3- 二极环加成反应，并在此基础上用药效配体对其进行了修饰。
• Conjugation of indole derivatives by copper-catalyzed alkyne-azide cycloaddition
  作者：V. B. Sokolov、А. Yu. Aksinenko、Т. А. Epishina、Т. V. Goreva、S. О. Bachurin

  DOI：10.1007/s11172-017-1931-4

  日期：2017.9

  An efficient synthetic procedure to combine biologically active indole derivatives by the triazole-containing spacer in a molecule has been proposed. The procedure was based on a copper-catalyzed alkyne-azide cycloaddition of azide-containing carbazoles and N-propargyl-containing carbazoles, tetrahydrocarbazoles, and tetrahydro-γ-carbolines.

  已经提出了一种通过分子中含有三唑的间隔物结合生物活性吲哚衍生物的有效合成方法。该程序基于铜催化的含叠氮咔唑和含 N-炔丙基的咔唑、四氢咔唑和四氢-γ-咔啉的炔-叠氮环加成反应。
• Tetracyclic compounds
  申请人：HUNG David T.

  公开号：US20090239854A1

  公开（公告）日：2009-09-24

  This disclosure relates to new tetracyclic compounds that may be used to modulate a histamine receptor in an individual. The compounds in one embodiment are tetracyclic [4,3-b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

  本公开涉及新的四环化合物，可用于调节个体中的组胺受体。在一种实施例中，该化合物为四环[4,3-b]吲哚。还提供了包含该化合物的药物组合物，以及使用该化合物进行各种治疗应用的方法，包括治疗认知障碍、精神障碍、神经递质介导的障碍和/或神经元障碍。