N-(3-(piperazin-1-yl)propyl)-1,2,3,4-tetrahydroacridin-9-amine | 1489102-49-9

• 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-(3-(piperazin-1-yl)propyl)-1,2,3,4-tetrahydroacridin-9-amine
• CAS: 1489102-49-9
• 化学式: C₂₀H₂₈N₄
• 分子量: 324.469
• InChiKey: FTMVRAHXTOHIPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.82
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  40.19
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(3-(piperazin-1-yl)propyl)-1,2,3,4-tetrahydroacridin-9-amine 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  一种Aβ寡聚化抑制剂、合成方法及应用

  摘要：

  本发明公开一种Aβ寡聚化抑制剂、合成方法及应用，所述Aβ寡聚化抑制剂结构通式如下：其中，R1是氢、直链状烷基、支链状烷基、烷氧基、卤素、苯环、六元杂芳环、五元杂芳环、七元芳环、萘、蒽、萘醌、多芳环体系及其取代物中的一种；R2是氢、羧基、硝基、磺酸基、胺基、磷酸基及其取代物中的一种；n1＝1～4，n2＝1～4。本发明所提供的Aβ寡聚化抑制剂是基于Aβ寡聚过程特征、天然药效团和其他关键酶活性中心结构设计的，结构新颖、活性显著，以SN2反应为主即可完成合成，本发明合成方法路线简单可靠、收率高，更适合大规模制备。本发明的Aβ寡聚化抑制剂可广泛用于Aβ寡聚化抑制剂类抗AD药物和Aβ寡聚化相关检测、诊断试剂盒等。

  公开号：

  CN106883214B
• 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-(3-(piperazin-1-yl)propyl)-1,2,3,4-tetrahydroacridin-9-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.
• Design, synthesis, and biological evaluation of novel donepezil-tacrine hybrids as multi-functional agents with low neurotoxicity against Alzheimer’s disease
  作者：Ningwei Wang、Wenlong Jia、Junqin Wang、Zejun Yang、Yaoyang Liu、Dehua Huang、Xiaohan Mei、Xinxin Xiong、Jing Shi、Yadong Tang、Guang Chen、Donghua Di、Yunlei Hou、Yajing Liu

  DOI：10.1016/j.bioorg.2023.107010

  日期：2024.2