tert-butyl 4-(5-bromo-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate | 886361-90-6

• 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: tert-butyl 4-(5-bromo-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate
• 英文别名: tert-Butyl 4-(5-bromo-1H-indol-3-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate；tert-butyl 4-(5-bromo-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 886361-90-6
• 化学式: C₁₈H₂₁BrN₂O₂
• 分子量: 377.281
• InChiKey: HVSRIJCRJQQFJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 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
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(5-bromo-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate 在 platinum(IV) oxide 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 1.08h， 生成 Tert-butyl 4-(5-bromo-1-methylindol-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins

  摘要：

  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。

  公开号：

  US20110280808A1
• 作为产物：
  描述：

  5-溴吲哚 、 N-叔丁氧羰基-4-哌啶酮 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以86%的产率得到tert-butyl 4-(5-bromo-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate
  参考文献：
  名称：

  发现和表征新型的吲哚和7-氮杂吲哚衍生物作为β-淀粉样蛋白42聚集的抑制剂，用于治疗阿尔茨海默氏病。

  摘要：

  淀粉状蛋白-β肽聚集为细胞毒性寡聚体和原纤维聚集体被认为是阿尔茨海默病的主要病理事件之一。在这里，我们报告设计和合成一系列新的吲哚和7-氮杂吲哚衍生物，它们在3位上含有腈，哌啶和N-甲基-哌啶取代基，以防止淀粉样β的病理自组装。我们进一步证明，为了获得具有改善的理化特性以允许脑渗透的化合物，需要在3个位置取代氮杂吲哚和吲哚衍生物。

  DOI：

  10.1016/j.bmcl.2017.02.001

文献信息

• [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。
• N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists
  作者：Derek C. Cole、John W. Ellingboe、William J. Lennox、Hossein Mazandarani、Deborah L. Smith、Joseph R. Stock、Guoming Zhang、Ping Zhou、Lee E. Schechter

  DOI：10.1016/j.bmcl.2004.10.064

  日期：2005.1

  A series of Ni-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)indole derivatives was designed and synthesized. These compounds were shown to have high affinity for the 5-HT6 receptor. Two analogs, 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-1-sulfonyl]-phenylamine 15g and 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-5-methoxy-1H-indole-1-sulfonyl]-phenylamine 15y, had 0.4 and 3.0nM affinity, respectively, and antagonized the production of adenylate cyclase at sub-nanomolar concentrations. (C) 2004 Elsevier Ltd. All rights reserved.
• 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。
• Discovery and characterization of novel indole and 7-azaindole derivatives as inhibitors of β-amyloid-42 aggregation for the treatment of Alzheimer’s disease
  作者：Nampally Sreenivasachary、Heiko Kroth、Pascal Benderitter、Anne Hamel、Yvan Varisco、David T. Hickman、Wolfgang Froestl、Andrea Pfeifer、Andreas Muhs

  DOI：10.1016/j.bmcl.2017.02.001

  日期：2017.3

  design and synthesis of a novel series of indole and 7-azaindole derivatives containing, nitrile, piperidine and N-methyl-piperidine substituents at the 3-position to prevent the pathological self-assembly of amyloid-β. We have further demonstrated that substitution of the azaindole and indole derivatives at the 3 positions is required to obtain compounds with improved physicochemical properties to allow

  淀粉状蛋白-β肽聚集为细胞毒性寡聚体和原纤维聚集体被认为是阿尔茨海默病的主要病理事件之一。在这里，我们报告设计和合成一系列新的吲哚和7-氮杂吲哚衍生物，它们在3位上含有腈，哌啶和N-甲基-哌啶取代基，以防止淀粉样β的病理自组装。我们进一步证明，为了获得具有改善的理化特性以允许脑渗透的化合物，需要在3个位置取代氮杂吲哚和吲哚衍生物。