2-(piperazin-1-yl)-N-(1,2,3,4-tetrahydro-acridin-9-yl)acetamide

• 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: 2-(piperazin-1-yl)-N-(1,2,3,4-tetrahydro-acridin-9-yl)acetamide
• 英文别名: 2-piperazin-1-yl-N-(1,2,3,4-tetrahydroacridin-9-yl)acetamide
• 化学式: C₁₉H₂₄N₄O
• 分子量: 324.426
• InChiKey: MWKCDNFJTHGYJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  57.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-(6-bromohexyloxy)-4-methyl-2H-chromen-2-one 、 2-(piperazin-1-yl)-N-(1,2,3,4-tetrahydro-acridin-9-yl)acetamide 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 8.0h， 以41%的产率得到2-(4-(6-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)hexyl)piperazin-1-yl)-N-(1,2,3,4-tetrahydroacridin-9-yl)acetamide
  参考文献：
  名称：

  Design, synthesis and evaluation of novel tacrine–coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease

  摘要：

  A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced,beta-amyloid (A beta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 mu M) and A beta aggregation (67.8%, 20 mu M). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 mu M) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.051
• 作为产物：
  描述：

  9-胺-1,2,3,4-四氢盐酸氯酯 在 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-(piperazin-1-yl)-N-(1,2,3,4-tetrahydro-acridin-9-yl)acetamide
  参考文献：
  名称：

  作为抗阿尔茨海默病多功能候选药物的新型他克林-阿魏酸杂合体的设计、合成和评价

  摘要：

  合成了五种新型他克林-阿魏酸杂化化合物（8a-e），并在详细光谱分析的基础上鉴定了它们的结构。在体外评估了抑制乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE)、减少自诱导 β-淀粉样蛋白 (Aβ) 聚集和螯合 Cu2+ 的活性。其中，8c 和 8d 在抑制 AChE 方面表现出比 BuChE 更高的选择性。此外，8d 还显示出对自身 Aβ 聚集、螯合 Cu2+ 的活性和对 Neuro-2A 细胞中 Aβ 诱导的神经毒性的活性的显着抑制。

  DOI：

  10.3390/molecules21101338

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。
• Design, synthesis and evaluation of novel tacrine–coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease
  作者：Sai-Sai Xie、Xiao-Bing Wang、Jiang-Yan Li、Lei Yang、Ling-Yi Kong

  DOI：10.1016/j.ejmech.2013.03.051

  日期：2013.6

  A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced,beta-amyloid (A beta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 mu M) and A beta aggregation (67.8%, 20 mu M). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 mu M) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer’s Disease
  作者：Yingbo Fu、Yu Mu、Hui Lei、Pu Wang、Xin Li、Qiao Leng、Li Han、Xiaodan Qu、Zhanyou Wang、Xueshi Huang

  DOI：10.3390/molecules21101338

  日期：——

  Five novel tacrine-ferulic acid hybrid compounds (8a–e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu2+ were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity

  合成了五种新型他克林-阿魏酸杂化化合物（8a-e），并在详细光谱分析的基础上鉴定了它们的结构。在体外评估了抑制乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE)、减少自诱导 β-淀粉样蛋白 (Aβ) 聚集和螯合 Cu2+ 的活性。其中，8c 和 8d 在抑制 AChE 方面表现出比 BuChE 更高的选择性。此外，8d 还显示出对自身 Aβ 聚集、螯合 Cu2+ 的活性和对 Neuro-2A 细胞中 Aβ 诱导的神经毒性的活性的显着抑制。