ethyl 8-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate | 63277-57-6

• 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
• 英文名称: ethyl 8-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate
• 英文别名: 8-bromo-2-ethoxycarbonyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole；ethyl 8-bromo-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate；2-carbethoxy-8-bromo-1,2,3,4-tetrahydropyrido[4,3-b]indole；ethyl 8-bromo-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylate
• CAS: 63277-57-6
• 化学式: C₁₄H₁₅BrN₂O₂
• mdl: MFCD16618489
• 分子量: 323.189
• InChiKey: MHGMMWXVHWEKHX-UHFFFAOYSA-N

物化性质

• 熔点：
  193 °C(Solv: ethanol (64-17-5))
• 沸点：
  463.4±45.0 °C(Predicted)
• 密度：
  1.538±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  ethyl 8-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate 在 乙醇 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 potassium hydroxide 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.0h， 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
• 作为产物：
  描述：

  4-溴苯胺 在 盐酸 、 tin(II) chloride dihdyrate 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 3.75h， 生成 ethyl 8-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate
  参考文献：
  名称：

  支架跳跃法设计和合成抗真菌苯并杂环衍生物

  摘要：

  侵袭性真菌感染的发生率和相关死亡率急剧增加。尽管唑类是一线抗真菌剂，但交叉耐药性和肝毒性是它们的两个主要限制。新型非唑类铅化合物的发现将有助于克服这些问题。根据我们先前报道的苯并吡喃非唑CYP51抑制剂，使用脚手架跳跃来设计结构多样的新化合物并扩展前导结构的构效关系。选择了五种支架，即苯并咪唑，苯并恶唑，苯并噻唑，喹唑啉-4-酮和咔啉。体外抗真菌活性数据和分子对接的结果表明，支架对抗真菌活性很重要。

  DOI：

  10.1016/j.ejmech.2011.01.075

文献信息

• Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins
  申请人：Kroth Heiko

  公开号：US20110280808A1

  公开（公告）日：2011-11-17

  The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

  本发明涉及一种新型化合物，可用于治疗与淀粉样蛋白相关的一组疾病和异常，如阿尔茨海默病，以及与淀粉样蛋白类似蛋白相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织中的病理异常/变化相关的眼部疾病。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于治疗或预防与淀粉样和/或淀粉样类似蛋白相关的疾病或病况的药物的用途。还公开了一种治疗或预防与淀粉样和/或淀粉样类似蛋白相关的疾病或病况的方法。
• [EN] NOVEL COMPOUNDS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS<br/>[FR] NOUVEAUX COMPOSÉS POUR LE TRAITEMENT DE MALADIES ASSOCIÉES AUX PROTÉINES AMYLOÏDES OU DE TYPE AMYLOÏDE
  申请人：AC IMMUNE SA

  公开号：WO2011128455A1

  公开（公告）日：2011-10-20

  The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

  本发明涉及一类新化合物，可用于治疗与淀粉样蛋白相关的一组疾病和异常，例如阿尔茨海默病，以及与类淀粉样蛋白相关的疾病或状况。本发明的化合物还可用于治疗与视觉系统组织病理性异常/变化相关的眼病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物制备用于治疗或预防与淀粉样和/或类淀粉样蛋白相关的疾病或状况的药物。还公开了一种治疗或预防与淀粉样和/或类淀粉样蛋白相关疾病或状况的方法。
• Enantioselective synthesis of <i>cis</i>-hexahydro-<i>γ</i>-carboline derivatives <i>via</i> Ir-catalyzed asymmetric hydrogenation
  作者：Long-Sheng Zheng、Congcong Yin、Fangyuan Wang、Gen-Qiang Chen、Xumu Zhang

  DOI：10.1039/d1cc06888a

  日期：——

  A novel synthetic route was developed for the construction of a chiral cis-hexahydro-γ-carboline derivative through Ir/ZhaoPhos-catalyzed asymmetric hydrogenation of corresponding tetrahydro-γ-carboline with high yields (up to 99% yield), excellent diastereoselectivities (up to >99 : 1 dr) and enantioselectivities (up to 99% ee), and high substrate-to-catalyst ratios (up to 5000).

  开发了一种新的合成路线，用于通过 Ir/ZhaoPhos 催化相应四氢-γ-咔啉的不对称氢化构建手性顺式-六氢-γ-咔啉衍生物，收率高（收率高达 99%），具有优异的非对映选择性（高达至 >99 : 1 dr）和对映选择性（高达 99% ee），以及高底物催化剂比（高达 5000）。
• Synthesis of 8-substituted tetrahydro-γ-carbolines
  作者：Alexandre Bridoux、Laurence Goossens、Raymond Houssin、Jean-Pierre Héanichart

  DOI：10.1002/jhet.5570430308

  日期：2006.5

  The Fischer reaction is applied to the synthesis of 8-substituted tetrahydro-γ-carbolines with electron-donating or electron-withdrawing groups, using catalytic or thermal methods. The reaction conditions must be varied according to the nature of the N 1 substituent of the piperidone. The best results are observed when a releasing group is present on the arylhydrazine and a benzyl substituent on the

  使用催化或热方法，将Fischer反应应用于具有供电子或吸电子基团的8-取代的四氢-γ-咔啉的合成。反应条件必须根据哌啶酮的N 1取代基的性质而变化。当芳基肼上的释放基团和哌啶酮的氮上的苄基取代基存在时，观察到最好的结果。在软酸性条件下观察到带有取代基的咔啉的形成；在其他情况下，反应在ended水平结束或没有发生。
• [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。