5,7-dichloro-2-(5-hydroxy-1H-indol-2-yl)quinolin-8-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5,7-dichloro-2-(5-hydroxy-1H-indol-2-yl)quinolin-8-ol
• 化学式: C₁₇H₁₀Cl₂N₂O₂
• 分子量: 345.185
• InChiKey: BUZJBPZCWKLESY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,7-dichloro-2-(5-hydroxy-1H-indol-2-yl)quinolin-8-ol 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 12.0h， 以97%的产率得到5,7-dichloro-2-(5-hydroxy-1H-indol-2-yl)quinolin-8-ol hydrochloride
  参考文献：
  名称：

  喹啉-吲哚衍生物及其在制备治疗阿尔茨海默 病的药品中的应用

  摘要：

  本发明公开了一种喹啉‑吲哚衍生物及其在制备治疗、改善和/或预防阿尔茨海默病的药品中的应用。本发明的喹啉‑吲哚衍生物是多靶点抗阿尔茨海默病活性分子，具有诱导神经细胞PC12神经元数目增加、神经元分化、抗氧化、抑制Aβ聚集和解聚作用，可以促成年小鼠大脑海马区神经元形成、长期性口服具有改善阿尔兹海默病小鼠APP/PS1认知能力及空间记忆。

  公开号：

  CN107778282B
• 作为产物：
  描述：

  5,7-二氯-8-羟基喹哪啶 在 1,10-菲罗啉 、 一氧化碳 、 sodium methylate 、 palladium diacetate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~150.0 ℃ 、4.0 MPa 条件下， 反应 25.0h， 生成 5,7-dichloro-2-(5-hydroxy-1H-indol-2-yl)quinolin-8-ol
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Bioavailable Quinoline–Indole Derivatives as Innovative Multitarget-Directed Ligands: Promotion of Cell Proliferation in the Adult Murine Hippocampus for the Treatment of Alzheimer’s Disease

  摘要：

  A novel series of quinoline-indole derivatives were synthesized and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease (AD). Biological evaluation revealed that the derivatives had multifunctional profiles including antioxidant effects, blood-brain barrier (BBB) penetration, biometal chelation, A beta aggregation modulation, neurotrophic and neuroprotective properties. Moreover, several representative target derivatives demonstrated hippocampal cell proliferation in living adult mice by intracerebroventricular (icv) injection or oral administration. Further drug-like property analysis demonstrated that the optimized compound, 8d (WI-1758), had liver microsomal metabolic stability, was well tolerated (>2000 mg/kg), and had a rational pharmacokinetic profile, as well as an oral bioavailability of 14.1% and a positive log BB (-0.19) to cross the BBB in vivo. Pharmacodynamics studies demonstrated that chronic oral administration of 8d center dot HCl substantially ameliorated the cognitive and spatial memory deficits in APP/PS1 AD mice and noticeably reduced overall cerebral beta-amyloid deposits.

  DOI：

  10.1021/acs.jmedchem.7b01417

文献信息

• 喹啉-吲哚衍生物及其在制备治疗阿尔茨海默 病的药品中的应用
  申请人：中山大学

  公开号：CN107778282B

  公开（公告）日：2020-04-10

  本发明公开了一种喹啉‑吲哚衍生物及其在制备治疗、改善和/或预防阿尔茨海默病的药品中的应用。本发明的喹啉‑吲哚衍生物是多靶点抗阿尔茨海默病活性分子，具有诱导神经细胞PC12神经元数目增加、神经元分化、抗氧化、抑制Aβ聚集和解聚作用，可以促成年小鼠大脑海马区神经元形成、长期性口服具有改善阿尔兹海默病小鼠APP/PS1认知能力及空间记忆。
• Design, Synthesis, and Evaluation of Orally Bioavailable Quinoline–Indole Derivatives as Innovative Multitarget-Directed Ligands: Promotion of Cell Proliferation in the Adult Murine Hippocampus for the Treatment of Alzheimer’s Disease
  作者：Zhiren Wang、Jinhui Hu、Xiaoping Yang、Xing Feng、Xingshu Li、Ling Huang、Albert S. C. Chan

  DOI：10.1021/acs.jmedchem.7b01417

  日期：2018.3.8

  A novel series of quinoline-indole derivatives were synthesized and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease (AD). Biological evaluation revealed that the derivatives had multifunctional profiles including antioxidant effects, blood-brain barrier (BBB) penetration, biometal chelation, A beta aggregation modulation, neurotrophic and neuroprotective properties. Moreover, several representative target derivatives demonstrated hippocampal cell proliferation in living adult mice by intracerebroventricular (icv) injection or oral administration. Further drug-like property analysis demonstrated that the optimized compound, 8d (WI-1758), had liver microsomal metabolic stability, was well tolerated (>2000 mg/kg), and had a rational pharmacokinetic profile, as well as an oral bioavailability of 14.1% and a positive log BB (-0.19) to cross the BBB in vivo. Pharmacodynamics studies demonstrated that chronic oral administration of 8d center dot HCl substantially ameliorated the cognitive and spatial memory deficits in APP/PS1 AD mice and noticeably reduced overall cerebral beta-amyloid deposits.