8-溴-2-甲基-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 | 5055-01-6

• 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
• 中文名称: 8-溴-2-甲基-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚
• 中文别名: 8-溴-1-甲基-2,3,4,5-四氢-1H-吡啶并[4,3-B]吲哚
• 英文名称: 8-bromo-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
• 英文别名: 8-bromo-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole；8-Brom-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol；2-methyl-8-bromo-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole；8-bromo-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole；2-Methyl-8-brom-2,3,4,5-tetrahydro-1H-pyrido<4,3-b>indol；8-bromo-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole
• CAS: 5055-01-6
• 化学式: C₁₂H₁₃BrN₂
• mdl: MFCD00266736
• 分子量: 265.153
• InChiKey: HFILMDDJKHXWEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  8-溴-2-甲基-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 在 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 9-bromo-2,3-dimethyl-1,4,5,6-tetrahydrodiazepino[5,4-b]indole
  参考文献：
  名称：

  经由叶立德中间体将四氢-γ-咔啉转化为六氢[1,2]二氮杂[5,4- b ]吲哚。9-溴-2,3-二甲基-1,2,3,4,5,6-六氢[1,2]二氮杂[5,4- b ]吲哚的X射线晶体结构测定

  摘要：

  Ñ的2-甲基-2,3,4,5-四氢-1H-1 -Amination ħ -吡啶并[4,3- b ]吲哚用ñ -烷基- ö -tosylhydroxylamines随后碱处理，得到1,2,3,4- ，5,6-六氢-2,3-二烷基[1,2]二氮杂[5,4- b ]吲哚，其中之一的结构由光谱证据和X射线结构分析确定。

  DOI：

  10.1039/p19830001937
• 作为产物：
  描述：

  4-溴苯肼盐酸盐 在 乙醇 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 28.0h， 生成 8-溴-2-甲基-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚
  参考文献：
  名称：

  Functionalized tetrahydro-1H-pyrido[4,3-b]indoles: A novel chemotype with Sirtuin 2 inhibitory activity

  摘要：

  Sirtuins are protein deacylases with regulatory roles in metabolism and stress response. Functionalized tetrahydro-1H-pyrido[4,3-b]indoles were identified as preferential sirtuin 2 inhibitors, with in vitro inhibitory potencies in the low micromolar concentrations (IC50 3-4 mu M) for the more promising candidates. The functional relevance of sirtuin inhibition was corroborated in western blots that showed hyperacetylation of p53 and alpha-tubulin in treated HepG2 and MDA-MB-231 cells. Molecular docking showed that the tetrahydropyridoindole scaffold was positioned in the NAD + pocket and the acetylated substrate channel of the sirtuin 2 protein by van der Waals/hydrophobic, H bonding and stacking interactions. Functionalized tetrahydropyridoindoles represent a novel class of sirtuin 2 inhibitors that could be further explored for its therapeutic potential. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.027

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。
• Synthesis and biological evaluation of novel γ-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists
  作者：Alexandre V. Ivachtchenko、Eugene B. Frolov、Oleg D. Mitkin、Volodymyr M. Kysil、Alexander V. Khvat、Ilya M. Okun、Sergey E. Tkachenko

  DOI：10.1016/j.bmcl.2009.04.128

  日期：2009.6

  Synthesis, biological evaluation and structure–activity relationships for a series of novel γ-carboline analogues of Dimebon™ are described. Among the studied compounds, γ-carbolines 38} and 314} have been identified as potent small molecule antagonists of histamine H1 (IC50 = 0.1 μM) and serotonin 5-HT6 (IC50 = 0.37 μM) receptors, respectively.

  描述了一系列新的Dimebon ™ γ-咔啉类似物的合成，生物学评估和结构-活性关系。在研究的化合物中，已确定γ-咔啉3 8}和3 14 }是组胺H 1（IC 50  = 0.1μM）和5-羟色胺5-HT 6（IC 50  = 0.37μM）受体的有效小分子拮抗剂。， 分别。
• [EN] METHODS FOR PREPARING PYRIDYLETHYL-SUBSTITUTED CARBOLINES<br/>[FR] PROCÉDÉS POUR PRÉPARER DES CARBOLINES SUBSTITUÉES PAR PYRIDYLÉTHYLE
  申请人：MEDIVATION NEUROLOGY INC

  公开号：WO2009111540A1

  公开（公告）日：2009-09-11

  Methods of preparing pyridylethyl-substituted carbolines under reaction conditions that use fewer molar equivalents of MVP to produce the pyridylethyl-substituted carboline as compared to reported methods of preparing pyridylethyl-substituted carbolines using MVP are provided. Also provided are methods of preparing a pyridylethyl-substituted carboline using non-commercial MVP.

  提供了一种在反应条件下制备吡啶乙基取代的咔啉类化合物的方法，该方法使用较少的MVP摩尔当量来生产吡啶乙基取代的咔啉类化合物，与使用MVP制备吡啶乙基取代的咔啉类化合物的报道方法相比。还提供了使用非商业MVP制备吡啶乙基取代的咔啉类化合物的方法。
• Methods and compositions for treating Huntington's disease
  申请人：Hung David

  公开号：US20070117834A1

  公开（公告）日：2007-05-24

  The invention provides method for treating Huntington's disease, slowing the onset and/or development and/or progression of Huntington's disease or preventing the development of Huntington's disease using hydrogenated pyrido[4,3-b]indoles, including dimebon.

  这项发明提供了一种治疗亨廷顿病的方法，通过使用氢化吡啶并呋[4,3-b]吲哚类化合物，包括二甲苯胺，来减缓亨廷顿病的发病、发展和/或进展，或预防亨廷顿病的发展。
• METHODS AND COMBINATION THERAPIES FOR TREATING ALZHEIMER'S DISEASE
  申请人：Hung David T.

  公开号：US20100152108A1

  公开（公告）日：2010-06-17

  The invention provides methods and combination therapies for treating and/or preventing and/or slowing the onset and/or development of Alzheimer's disease using a hydrogenated pyrido (4,3-b) indole (e.g., dimebon) in conjunction with another compound, pharmaceutically acceptable salt thereof or therapy for Alzheimer's disease.

  该发明提供了一种治疗和/或预防和/或减缓阿尔茨海默病的发作和/或发展的方法和联合疗法，使用氢化吡啶并哌啶(例如二甲苯胺)与另一化合物、其药用盐或治疗阿尔茨海默病的疗法结合。