7-methoxy-1,2,3,4-tetrahydroacridin-9(10H)-one | 151921-07-2

• 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: 7-methoxy-1,2,3,4-tetrahydroacridin-9(10H)-one
• 英文别名: 7-methoxy-1,2,3,4-tetrahydroacridin-10H-9-one；7-methoxy-2,3,4,10-tetrahydro-1H-acridin-9-one
• CAS: 151921-07-2
• 化学式: C₁₄H₁₅NO₂
• mdl: MFCD09248457
• 分子量: 229.279
• InChiKey: NAKOPQZYTOAWQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  424.7±45.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-methoxy-1,2,3,4-tetrahydroacridin-9(10H)-one 在 三氯氧磷 、 苯酚 作用下， 生成 N-(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl)butane-1,4-diamine
  参考文献：
  名称：

  7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer’s Disease Treatment — Synthesis, Biological Evaluation and Molecular Modeling Studies

  摘要：

  作为人乙酰胆碱酯酶（hAChE）和人丁酰胆碱酯酶（hBChE）的抑制剂，我们设计、合成并评估了一系列 7-MEOTA- 金刚烷胺硫脲类化合物。这些化合物是根据多靶点定向配体策略制备的，其中著名的 NMDA 拮抗剂金刚烷和 hAChE 抑制剂 7-甲氧基他克林（7-MEOTA）连接了不同长度（n = 2-8 ）的连接体。根据硅学研究，这些抑制剂具有双重结合位点特性，能够同时与 hAChE 的外周阴离子位点（PAS）和催化活性位点（CAS）相互作用。显然，这些结构衍生物对 hBChE 具有很好的抑制活性，从而产生了更具选择性的该酶抑制剂。最有效的胆碱酯酶抑制剂是硫脲类似物 14（对 hAChE 的 IC50 值为 0.47 µM，对 hBChE 的 IC50 值为 0.11 µM）。分子 14 是一个适合进一步评估的新型先导化合物，证明了双结合位点抑制剂的策略可能是开发新型抗抑郁药物的一个有前途的方向。

  DOI：

  10.3390/molecules18022397
• 作为产物：
  描述：

  9-chloro-7-methoxy-1,2,3,4-tetrahydroacridine 在 溶剂黄146 作用下， 生成 7-methoxy-1,2,3,4-tetrahydroacridin-9(10H)-one
  参考文献：
  名称：

  Optimization of 1,2,3,4-Tetrahydroacridin-9(10H)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships

  摘要：

  Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.

  DOI：

  10.1021/jm200015a

文献信息

• Auto-tandem PET and EnT photocatalysis by crude chlorophyll under visible light towards the oxidative functionalization of indoles
  作者：Saira Banu、Shubham Choudhari、Girija Patel、Prem P. Yadav

  DOI：10.1039/d1gc00138h

  日期：——

  Chlorophyll is the most abundant photocatalytic pigment that enables plants to absorb solar energy and convert it to energy storage molecules. Herein, we report a tandem photocatalytic approach utilizing the natural pigment chlorophyll in crude form to achieve photoinduced electron transfer (PET) and energy transfer (EnT) towards the oxidative functionalization of indoles. Redox potentials, ESR, fluorescence

  叶绿素是最丰富的光催化颜料，使植物能够吸收太阳能并将其转化为能量存储分子。在本文中，我们报告了一种串联光催化方法，该方法利用天然形式的天然色素叶绿素实现了对吲哚的氧化功能化的光致电子转移（PET）和能量转移（EnT）。氧化还原电势，ESR，荧光猝灭和紫外线实验已经证明了叶绿素的双重催化活性。该研究的重点是叶绿素的自动串联光催化作用，以分子氧作为氧化剂，水作为反应介质，并利用光谱可见区的光化学能，使吲哚绿色氧化。
• 7-MEOTA–donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies
  作者：Jan Korabecny、Rafael Dolezal、Pavla Cabelova、Anna Horova、Eva Hruba、Jan Ricny、Lukas Sedlacek、Eugenie Nepovimova、Katarina Spilovska、Martin Andrs、Kamil Musilek、Veronika Opletalova、Vendula Sepsova、Daniela Ripova、Kamil Kuca

  DOI：10.1016/j.ejmech.2014.05.066

  日期：2014.7

  mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA–donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as

  合成了一系列新的类似7-甲氧基他克林（7-MEOTA）-多奈哌齐的化合物，并测试了它们抑制鳗鱼乙酰胆碱酯酶（Ee AChE），人重组AChE（h AChE），马血清丁酰胆碱酯酶（eq BChE）的能力。血浆BChE（h BChE）。新杂种由一个7 MEOTA单元，代表毒性较小他克林（THA）衍生物与类似物连接Ñ -benzylpiperazine部分模仿ñ从多奈哌齐苄基哌啶片段。7-MEOTA–多奈哌齐样化合物在抑制不同来源的胆碱酯酶（IC 50）方面表现出非选择性的特征范围从微摩尔到亚微摩尔浓度范围。动力学分析证实了混合型抑制作用，认为这些抑制剂能够同时结合AChE的外围阴离子位点（PAS）和催化阴离子位点（CAS）。进行了分子建模研究和QSAR研究，使体外研究合理化。总的来说，像7-MEOTA-多奈哌齐这样的衍生物可以被认为是阿尔茨海默氏病治疗的有趣候选物。
• 7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer’s Disease Treatment — Synthesis, Biological Evaluation and Molecular Modeling Studies
  作者：Katarina Spilovska、Jan Korabecny、Jan Kral、Anna Horova、Kamil Musilek、Ondrej Soukup、Lucie Drtinova、Zuzana Gazova、Katarina Siposova、Kamil Kuca

  DOI：10.3390/molecules18022397

  日期：——

  A structural series of 7-MEOTA-adamantylamine thioureas was designed, synthesized and evaluated as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The compounds were prepared based on the multi-target-directed ligand strategy with different linker lengths (n = 2–8) joining the well-known NMDA antagonist adamantine and the hAChE inhibitor 7-methoxytacrine (7-MEOTA). Based on in silico studies, these inhibitors proved dual binding site character capable of simultaneous interaction with the peripheral anionic site (PAS) of hAChE and the catalytic active site (CAS). Clearly, these structural derivatives exhibited very good inhibitory activity towards hBChE resulting in more selective inhibitors of this enzyme. The most potent cholinesterase inhibitor was found to be thiourea analogue 14 (with an IC50 value of 0.47 µM for hAChE and an IC50 value of 0.11 µM for hBChE, respectively). Molecule 14 is a suitable novel lead compound for further evaluation proving that the strategy of dual binding site inhibitors might be a promising direction for development of novel AD drugs.

  作为人乙酰胆碱酯酶（hAChE）和人丁酰胆碱酯酶（hBChE）的抑制剂，我们设计、合成并评估了一系列 7-MEOTA- 金刚烷胺硫脲类化合物。这些化合物是根据多靶点定向配体策略制备的，其中著名的 NMDA 拮抗剂金刚烷和 hAChE 抑制剂 7-甲氧基他克林（7-MEOTA）连接了不同长度（n = 2-8 ）的连接体。根据硅学研究，这些抑制剂具有双重结合位点特性，能够同时与 hAChE 的外周阴离子位点（PAS）和催化活性位点（CAS）相互作用。显然，这些结构衍生物对 hBChE 具有很好的抑制活性，从而产生了更具选择性的该酶抑制剂。最有效的胆碱酯酶抑制剂是硫脲类似物 14（对 hAChE 的 IC50 值为 0.47 µM，对 hBChE 的 IC50 值为 0.11 µM）。分子 14 是一个适合进一步评估的新型先导化合物，证明了双结合位点抑制剂的策略可能是开发新型抗抑郁药物的一个有前途的方向。
• Structure–activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors
  作者：Gregory D. Cuny、Maxime Robin、Natalia P. Ulyanova、Debasis Patnaik、Valerie Pique、Gilles Casano、Ji-Feng Liu、Xiangjie Lin、Jun Xian、Marcie A. Glicksman、Ross L. Stein、Jonathan M.G. Higgins

  DOI：10.1016/j.bmcl.2010.04.150

  日期：2010.6

  Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure-activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC(50) <60 nM) with 180fold selectivity over DYRK2. In addition, a moderately potent DYRK2 inhibitor (41, IC(50) <400 nM) with a 5.4-fold selectivity over haspin was also identified. (C) 2010 Elsevier Ltd. All rights reserved.
• Del Giudice; Borioni; Mustazza, Il Farmaco, 1996, vol. 51, # 11, p. 693 - 698
  作者：Del Giudice、Borioni、Mustazza、Gatta、Meneguz、Volpe

  DOI：——

  日期：——