N-(piperazinoethyl)-N-(1,2,3,4-tetrahydroacridin-9-yl)amine | 1108149-32-1

• 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: N-(piperazinoethyl)-N-(1,2,3,4-tetrahydroacridin-9-yl)amine
• 英文别名: N-(2-(piperazin-1-yl)ethyl)-1,2,3,4-tetrahydroacridin-9-amine；N-(2-piperazin-1-ylethyl)-1,2,3,4-tetrahydroacridin-9-amine
• CAS: 1108149-32-1
• 化学式: C₁₉H₂₆N₄
• 分子量: 310.442
• InChiKey: ALBLVLIIOKNDOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  40.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(piperazinoethyl)-N-(1,2,3,4-tetrahydroacridin-9-yl)amine 在 氨 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 1.0h， 生成 3-[cyclohexyl(ethyl)amino]-1-{4-[2-(1,2,3,4-tetrahydroacridin-9-ylamino)ethyl]piperazino}-1-propanone
  参考文献：
  名称：

  用于治疗阿尔茨海默氏病的新型高效他克林同源物的合成，设计和生物学评估

  摘要：

  合成了新的他克林衍生物5a - d，6a - d和哌嗪子乙基间隔物并连接了相应的仲胺和他克林同二聚体8，并作为人乙酰胆碱酯酶（h AChE）和人血浆丁酰胆碱酯酶（h BChE）的胆碱酯酶抑制剂进行了测试。在大多数情况下，大多数合成衍生物表现出较高的AChE和BChE抑制活性，IC 50值在低纳摩尔范围内，明显比参考标准他克林（9-氨基-1,2,3,4-四氢ac啶，1）和7-MEOTA（7-甲氧基-9-氨基-1,2,3,4-四氢ac啶）。其中，抑制剂图8和5c显示出对h AChE的强抑制活性，IC 50值为4.49 nM和4.97，nM分别，并且对h AChE具有高选择性。化合物5d以hIC 50值为33.7 nM充当h BChE的最有效抑制剂，并且还表现出对h BChE的良好选择性。将所选抑制剂的解离常数K i与它们的IC 50值进行比较。进行分子建模研究以预测单个衍生物与h AChE /

  DOI：

  10.1016/j.ejmech.2012.06.051
• 作为产物：
  描述：

  环己酮 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 14.0h， 生成 N-(piperazinoethyl)-N-(1,2,3,4-tetrahydroacridin-9-yl)amine
  参考文献：
  名称：

  Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease

  摘要：

  A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 mu M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.040

文献信息

• 一种他克林-8-羟（胺）基喹啉衍生物及其应用
  申请人：广东工业大学

  公开号：CN105367553A

  公开（公告）日：2016-03-02

  本发明涉及一种他克林-8-羟（胺）基喹啉衍生物及其应用，属于生物医药技术领域；该衍生物包括式I化合物及其药学上适用的盐；其制备方法是将化合物Id和Ii与中间体In/In’经还原胺化、脱保护得到化合物I，在醇溶液中可反应制备成盐；经药理试验证实该类化合物具有抗阿茨海默症活性，能够抑制乙酰胆碱酯酶和丁酰胆碱酯酶活性，同时能够抑制β-淀粉样蛋白的自聚合并对金属离子特别是Cu2+、Zn2+具有一定的螯合作用，从而起到延缓乙酰胆碱的水解和β-淀粉样蛋白的自聚合，提高乙酰胆碱在突触的作用，并调节脑内金属离子，可有效用于治疗阿茨海默症。
• Multifunctional tacrine–flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease
  作者：Su-Yi Li、Xiao-Bing Wang、Sai-Sai Xie、Neng Jiang、Kelvin D.G. Wang、He-Quan Yao、Hong-Bin Sun、Ling-Yi Kong

  DOI：10.1016/j.ejmech.2013.09.024

  日期：2013.11

  A new series of tacrine flavonoid hybrids (13a u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-beta (A beta(1-42)) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced A beta(1-42) aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis, Structure, and Cholinergic Effect of Novel Neuroprotective Compounds Bearing the Tacrine Pharmacophore
  作者：Pavol Kristian、Slávka Hamul'aková、Daniel Jun、Kamil Kuca、Ján Imrich、Ivan Danihel、Stanislav Böhm、Karel D. Klika

  DOI：10.3987/com-08-s(n)83

  日期：——