7-((6-bromohexyl)oxy)-3-(4-((6-bromohexyl)oxy)phenyl)-5-hydroxy-4H-chromen-4-one | 1439920-43-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 7-((6-bromohexyl)oxy)-3-(4-((6-bromohexyl)oxy)phenyl)-5-hydroxy-4H-chromen-4-one
• CAS: 1439920-43-0
• 化学式: C₂₇H₃₂Br₂O₅
• 分子量: 596.356
• InChiKey: IFSQFDJJDPLBFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.83
• 重原子数：
  34.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  68.9
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-苄基哌嗪 、 7-((6-bromohexyl)oxy)-3-(4-((6-bromohexyl)oxy)phenyl)-5-hydroxy-4H-chromen-4-one 以 乙腈 为溶剂， 以59.2%的产率得到7-((6-(4-benzylpiperazin-1-yl)hexyl)oxy)-3-(4-((6-(4-benzylpiperazin-1-yl)hexyl)oxy)phenyl)-5-hydroxy-4H-chromen-4-one
  参考文献：
  名称：

  染料木黄酮-O-烷基胺衍生物作为治疗阿尔茨海默病的多功能药物的开发

  摘要：

  多靶点定向配体被认为是治疗阿尔茨海默病（AD）的有前途的多功能药物。基于我们之前的工作，开发了一系列染料木黄酮-O-烷基胺衍生物以进一步探索构效关系。结果表明，化合物7d具有可逆且高选择性的h AChE抑制活性，IC 50值为0.53 μM。化合物7d还显示出良好的抗氧化活性（ORAC = 1.1  eq.），具有良好的神经保护作用和选择性金属螯合特性。此外，化合物7d显着抑制了自诱导、hAChE 诱导的和 Cu 2+诱导的 A β聚集分别为 39.8%、42.1% 和 74.1%，并且解聚了Cu 2+诱导的 A β 1-42聚集（67.3%）。此外，化合物7d是一种潜在的自噬诱导剂，可提高 GPX4 蛋白的水平。此外，化合物7d在体外表现出良好的血脑屏障渗透性。更重要的是，化合物7d在高达 1000 mg/kg 的剂量下没有表现出任何急性毒性，并且对东莨菪碱诱导的记忆障碍具有良好的预知作

  DOI：

  10.1016/j.bioorg.2020.104602
• 作为产物：
  描述：

  1,6-二溴己烷 、 染料木素 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 7-((6-bromohexyl)oxy)-3-(4-((6-bromohexyl)oxy)phenyl)-5-hydroxy-4H-chromen-4-one
  参考文献：
  名称：

  染料木黄酮-O-烷基胺衍生物作为治疗阿尔茨海默病的多功能药物的开发

  摘要：

  多靶点定向配体被认为是治疗阿尔茨海默病（AD）的有前途的多功能药物。基于我们之前的工作，开发了一系列染料木黄酮-O-烷基胺衍生物以进一步探索构效关系。结果表明，化合物7d具有可逆且高选择性的h AChE抑制活性，IC 50值为0.53 μM。化合物7d还显示出良好的抗氧化活性（ORAC = 1.1  eq.），具有良好的神经保护作用和选择性金属螯合特性。此外，化合物7d显着抑制了自诱导、hAChE 诱导的和 Cu 2+诱导的 A β聚集分别为 39.8%、42.1% 和 74.1%，并且解聚了Cu 2+诱导的 A β 1-42聚集（67.3%）。此外，化合物7d是一种潜在的自噬诱导剂，可提高 GPX4 蛋白的水平。此外，化合物7d在体外表现出良好的血脑屏障渗透性。更重要的是，化合物7d在高达 1000 mg/kg 的剂量下没有表现出任何急性毒性，并且对东莨菪碱诱导的记忆障碍具有良好的预知作

  DOI：

  10.1016/j.bioorg.2020.104602

文献信息

• Design, synthesis and evaluation of genistein-O-alkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease
  作者：Xiaoming Qiang、Zhipei Sang、Wen Yuan、Yan Li、Qiang Liu、Ping Bai、Yikun Shi、Wei Ang、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.ejmech.2014.02.045

  日期：2014.4

  A series of genistein derivatives with carbon spacer-linked alkylbenzylamines were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good acetylcholinesterase (AChE) inhibitory activity, with moderate-to-good anti-oxidative activity. Specifically, compounds 10b, 19d and 254 exhibited significant inhibition of beta-amyloid (A beta) aggregation and exhibited metal chelating properties. In particular, 25d inhibited: self-induced A beta(1-42) aggregation, Cu2+-induced A beta(1-42) aggregation, and human AChE-induced A beta(1-40) aggregation by 35%, 77.8%, and 36.2%, respectively. Moreover, both kinetic analysis of AChE inhibition and the molecular modeling study suggested that 25d binds simultaneously to catalytic active site and peripheral anionic site of AChE. More importantly, compound 25d disassembled the well-structured A beta fibrils generated by Cu2+-induced A beta aggregation by 72.1%. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. These results suggest that 25d may be a promising multifunctional agent for AD treatment. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of genistein-<i>O</i> -alkylamine derivatives as potential multifunctional anti-Alzheimer agents
  作者：Chen Hong、Hui-yan Guo、Shuai Chen、Jian-wu Lv、Xin Zhang、Ya-cheng Yang、Kang Huang、Yi-juan Zhang、Zhi-yong Tian、Wen Luo、Yi-ping Chen

  DOI：10.1111/cbdd.13414

  日期：2019.2

  AbstractA series of genistein derivatives were synthesized and evaluated as multifunctional anti‐Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC50 value (0.034 μM) much lower than that of rivastigmine (6.53 μM). A Lineweaver–Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal‐chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 μM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.