2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)ethanamine | 1174729-49-7

• 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: 2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)ethanamine
• 英文别名: 2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)ethanamine
• CAS: 1174729-49-7
• 化学式: C₁₅H₂₁N₃
• 分子量: 243.352
• InChiKey: YQSTYMICAHDYJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)ethanamine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 aq. phosphate buffer 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 5-amino-N-[2-(2, 8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)ethyl]-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide

  摘要：

  Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain: plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.08.064
• 作为产物：
  描述：

  2,8-二甲基-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)ethanamine
  参考文献：
  名称：

  Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide

  摘要：

  Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain: plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.08.064

文献信息

• [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。
• 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。
• NEW 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Hung David T.

  公开号：US20100022580A1

  公开（公告）日：2010-01-28

  This disclosure relates to new tricyclic compounds that may be used to modulate a histamine receptor in an individual. Compounds are described, including new 2,3,4,5-tetrahydro- 1 H-pyrido[4,3-b]indole compounds. 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.

  本公开涉及新的三环化合物，可用于调节个体中的组胺受体。其中描述了化合物，包括新的2,3,4,5-四氢-1H-吡啶[4,3-b]吲哚化合物。还提供了包含该化合物的制药组合物，以及使用该化合物治疗各种治疗应用的方法，包括治疗认知障碍、精神病性障碍、神经递质介导的障碍和/或神经元障碍。
• TETRACYCLIC COMPOUNDS
  申请人：MEDIVATION TECHNOLOGIES, INC.

  公开号：US20140194414A1

  公开（公告）日：2014-07-10

  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.

  本文涉及新的四环化合物，可用于调节个体中的组胺受体。在其中一种实施方式中，这些化合物是四环[4,3-b]吲哚。还提供了包含这些化合物的制药组合物，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。
• 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Medivation Technologies, Inc.

  公开号：US20130190347A1

  公开（公告）日：2013-07-25

  This disclosure relates to new tricyclic compounds that may be used to modulate a histamine receptor in an individual. Compounds are described, including new 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole compounds. 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.

  本公开涉及新的三环化合物，可用于调节个体中的组胺受体。其中包括新的2,3,4,5-四氢-1H-吡啶[4,3-b]吲哚化合物。此外还提供了包含这些化合物的制药组合物，以及使用这些化合物治疗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。