5,7-dibromo-3,3-dimethyl-1,2,3,4-tetrahydro-1-acridinone

• 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: 5,7-dibromo-3,3-dimethyl-1,2,3,4-tetrahydro-1-acridinone
• 英文别名: 5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one；5,7-dibromo-3,3-dimethyl-3,4-idroacridin-1-(2H)-one；5,7-Dibromo-3,3-dimethyl-2,4-dihydroacridin-1-one
• 化学式: C₁₅H₁₃Br₂NO
• 分子量: 383.082
• InChiKey: FVZKSIFKCMSYLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,7-dibromo-3,3-dimethyl-1,2,3,4-tetrahydro-1-acridinone 、 盐酸氨基脲 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.17h， 以75%的产率得到(E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-ylidene)hydrazinecarboxamide
  参考文献：
  名称：

  New semicarbazones as gorge-spanning ligands of acetylcholinesterase and potential new drugs against Alzheimer’s disease: Synthesis, molecular modeling, NMR, and biological evaluation

  摘要：

  Two new compounds (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-ylidene)hydrazinecarbothiomide (3) and (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dhihydroacridin-1(2H)-ylidene) hydrazinecarboxamide (4) were synthesized and evaluated for their anticholinesterase activities. In vitro tests performed by NMR and Ellman's tests, pointed to a mixed kinetic mechanism for the inhibition of acetylcholinesterase (AChE). This result was corroborated through further docking and molecular dynamics studies, suggesting that the new compounds can work as gorge-spanning ligands by interacting with two different binding sites inside AChE. Also, in silico toxicity evaluation suggested that these new compounds can be less toxic than tacrine.

  DOI：

  10.1080/07391102.2017.1407676
• 作为产物：
  描述：

  2-氨基-3,5-二溴苯甲醛 、 5,5-二甲基-1,3-环己二酮 在 对甲苯磺酸 作用下， 反应 0.02h， 以96%的产率得到5,7-dibromo-3,3-dimethyl-1,2,3,4-tetrahydro-1-acridinone
  参考文献：
  名称：

  在无溶剂条件下，对甲苯磺酸辅助快速有效合成多取代喹啉：微波辐射与常规加热的比较研究。

  摘要：

  在对甲苯磺酸的存在下，通过2-氨基芳基酮或2-氨基芳基醛与羰基化合物的弗里德兰德缩合反应，已经开发出一种快速有效的制备各种多取代喹啉的方法，该方法通过微波辐射和微波辐射来实现。在无溶剂条件下进行常规加热。

  DOI：

  10.1039/b513721g

文献信息

• A Novel Enzymatic Synthesis of Quinoline Derivatives
  作者：Hui Zheng、Juan Liu、Yi Jia Mei、Qiao Yue Shi、Peng Fei Zhang

  DOI：10.1007/s10562-012-0774-8

  日期：2012.5

  A new mild enzymatic methodology for synthesizing quinoline derivatives by Friedländer condensation was developed. A series of quinoline derivatives were synthesized and characterized by 1H NMR, 13C-NMR, IR and MS. The probable enzymatic mechanism was proposed. It provides a novel method to prepare quinoline derivatives.Graphical Abstract 

  开发了一种新的温和酶促方法，用于通过 Friedländer 缩合合成喹啉衍生物。合成了一系列喹啉衍生物，并通过1H NMR、13C-NMR、IR和MS进行了表征。提出了可能的酶促机制。为喹啉衍生物的制备提供了一种新方法。 
• Rapid and efficient synthesis of poly-substituted quinolines assisted by p-toluene sulphonic acid under solvent-free conditions: comparative study of microwave irradiation versus conventional heating
  作者：Cheng-Sheng Jia、Ze Zhang、Shu-Jiang Tu、Guan-Wu Wang

  DOI：10.1039/b513721g

  日期：——

  A rapid and efficient method for the preparation of various poly-substituted quinolines has been developed through the Friedlander condensation of 2-aminoarylketone or 2-aminoarylaldehyde with carbonyl compounds in the presence of p-toluene sulphonic acid, which was achieved by both microwave irradiation and conventional heating under solvent-free conditions.

  在对甲苯磺酸的存在下，通过2-氨基芳基酮或2-氨基芳基醛与羰基化合物的弗里德兰德缩合反应，已经开发出一种快速有效的制备各种多取代喹啉的方法，该方法通过微波辐射和微波辐射来实现。在无溶剂条件下进行常规加热。
• A new guanylhydrazone derivative as a potential acetylcholinesterase inhibitor for Alzheimer's disease: synthesis, molecular docking, biological evaluation and kinetic studies by nuclear magnetic resonance
  作者：Denise Cristian Ferreira Neto、Marcelle de Souza Ferreira、Elaine da Conceição Petronilho、Josélia Alencar Lima、Sirlene Oliveira Francisco de Azeredo、Juliana de Oliveira Carneiro Brum、Claudia Jorge do Nascimento、José Daniel Figueroa Villar

  DOI：10.1039/c7ra04180b

  日期：——

  is associated with the memory loss. In this work, a new guanylhydrazone was designed and synthesized as an AChE inhibitor. This new compound was compared to tacrine and other guanylhydrazones. All of them were studied by molecular docking and tested in vitro as AChE inhibitors by Ellman's test and Fig-NMR method. A high inhibition of AChE by the new compound was observed, showing that this compound has

  由于这是痴呆症的最常见类型，因此开发用于治疗阿尔茨海默氏病（AD）的药物非常重要。抑制乙酰胆碱酯酶（AChE）对于增加在患者中观察到的低水平的乙酰胆碱（ACh）神经递质很重要，这与记忆力丧失有关。在这项工作中，设计并合成了一种新的胍hydr作为AChE抑制剂。将该新化合物与他克林和其他胍基compared进行了比较。所有这些均通过分子对接研究，并通过Ellman试验和Fig-NMR法在体外作为AChE抑制剂进行了测试。观察到新化合物对AChE的高度抑制作用，表明该化合物具有治疗AD的巨大潜力。
• New semicarbazones as gorge-spanning ligands of acetylcholinesterase and potential new drugs against Alzheimer’s disease: Synthesis, molecular modeling, NMR, and biological evaluation
  作者：Denise Cristian Ferreira Neto、Josélia Alencar Lima、Joyce Sobreiro Francisco Diz de Almeida、Tanos Celmar Costa França、Claudia Jorge do Nascimento、José Daniel Figueroa Villar

  DOI：10.1080/07391102.2017.1407676

  日期：2018.11.18

  Two new compounds (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-ylidene)hydrazinecarbothiomide (3) and (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dhihydroacridin-1(2H)-ylidene) hydrazinecarboxamide (4) were synthesized and evaluated for their anticholinesterase activities. In vitro tests performed by NMR and Ellman's tests, pointed to a mixed kinetic mechanism for the inhibition of acetylcholinesterase (AChE). This result was corroborated through further docking and molecular dynamics studies, suggesting that the new compounds can work as gorge-spanning ligands by interacting with two different binding sites inside AChE. Also, in silico toxicity evaluation suggested that these new compounds can be less toxic than tacrine.