2-(5-(4-benzylpiperazin-1-yl)pentyl)isoindoline-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(5-(4-benzylpiperazin-1-yl)pentyl)isoindoline-1,3-dione
• 英文别名: 2-[5-(4-Benzylpiperazin-1-yl)pentyl]isoindole-1,3-dione；2-[5-(4-benzylpiperazin-1-yl)pentyl]isoindole-1,3-dione
• 化学式: C₂₄H₂₉N₃O₂
• 分子量: 391.513
• InChiKey: CRYWXGXUEAFUOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,5-二溴戊烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 2-(5-(4-benzylpiperazin-1-yl)pentyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Development of Phthalimide-Donepezil Hybrids as Potent Multitarget- Directed Ligands for the Treatment of Alzheimer’s Disease

  摘要：

  背景：由于AD的复杂病因，多靶向配体（MTDLs），结合两种或更多不同的药理成分，已经在症状性和疾病修饰效率方面得到发展，并被认为是治疗AD的有效途径。 方法：为了测试它们的生物活性，包括AChE/BChE抑制活性和MAOA/MAO-B抑制活性。此外，进行了分子建模研究，以了解结合模式。 结果：结果显示，化合物4c显示出最佳的AChE抑制活性，IC50值为4.2μM，这得到了动力学研究和对接研究的支持。化合物4c也是选择性的MAO-B抑制剂（IC50 = 8.2μM）。此外，化合物4c在体外可以穿过血脑屏障。 结论：化合物4c值得进一步研究，作为治疗阿尔茨海默病的潜在多功能药物。

  DOI：

  10.2174/1570180817999200420120519

文献信息

• Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors
  作者：Weijie Si、Tao Zhang、Lanxiang Zhang、Xiangdong Mei、Mengya Dong、Kaixin Zhang、Jun Ning

  DOI：10.1016/j.bmcl.2015.07.052

  日期：2016.5

  A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44 nM and 13.58 nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study. (C) 2015 Elsevier Ltd. All rights reserved.
• Development of Phthalimide-Donepezil Hybrids as Potent Multitarget- Directed Ligands for the Treatment of Alzheimer’s Disease
  作者：Lintao Yu、Jian Shi、Xinfeng Cheng、Keren Wang、Shuang Liu、Wenmin Liu、Zhipei Sang

  DOI：10.2174/1570180817999200420120519

  日期：2020.9.11

  Due to the complex etiology of AD, multi-target-directed ligands (MTDLs), combining two or more distinct pharmacological moieties, have been developed in both symptomatic and disease-modifying efficiencies and are considered as an effective way for the treatment of AD.

  To test their biological activities, including AChE/BChE inhibitory activity and MAOA/ MAO-B inhibitory activity. In addition, molecular modeling studies were performed to afford insight into the binding mode.

  The results displayed that compound 4c showed the best AChE inhibitory activity with an IC50 value of 4.2 μM, which was supported by the kinetic study and docking study. Compound 4c was also a selective MAO-B inhibitor (IC50 = 8.2 μM). Moreover, compound 4c could cross the blood-brain barrier in vitro.

  Compound 4c deserved to further study as a potential multifunctional agent for the treatment of Alzheimer’s disease.

  背景：由于AD的复杂病因，多靶向配体（MTDLs），结合两种或更多不同的药理成分，已经在症状性和疾病修饰效率方面得到发展，并被认为是治疗AD的有效途径。 方法：为了测试它们的生物活性，包括AChE/BChE抑制活性和MAOA/MAO-B抑制活性。此外，进行了分子建模研究，以了解结合模式。 结果：结果显示，化合物4c显示出最佳的AChE抑制活性，IC50值为4.2μM，这得到了动力学研究和对接研究的支持。化合物4c也是选择性的MAO-B抑制剂（IC50 = 8.2μM）。此外，化合物4c在体外可以穿过血脑屏障。 结论：化合物4c值得进一步研究，作为治疗阿尔茨海默病的潜在多功能药物。