N-(3-bromo-4-methoxybenzylidene)-3,4,5-trimethoxyaniline | 1334595-10-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-bromo-4-methoxybenzylidene)-3,4,5-trimethoxyaniline
• CAS: 1334595-10-6
• 化学式: C₁₇H₁₈BrNO₄
• 分子量: 380.238
• InChiKey: LQTRHFYPUJYBOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.28
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(3-bromo-4-methoxybenzylidene)-3,4,5-trimethoxyaniline 在 盐酸肼 、 三乙胺 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 (3R,4R)-4-(3-bromo-4-methoxyphenyl)-3-hydroxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one
  参考文献：
  名称：

  Synthesis by diastereomeric resolution, biochemical evaluation and molecular modelling of chiral 3-hydroxyl b-lactam microtubule-targeting agents for the treatment of triple negative breast and chemoresistant colorectal cancers

  摘要：

  DOI：

  10.1016/j.bioorg.2023.106877
• 作为产物：
  描述：

  3-溴-4-甲氧基苯甲醛 、 3,4,5-三甲氧基苯胺 以 乙醇 为溶剂， 反应 6.0h， 生成 N-(3-bromo-4-methoxybenzylidene)-3,4,5-trimethoxyaniline
  参考文献：
  名称：

  通过抑制微管蛋白聚合并激活Hippo信号通路，在体外发现掺入苯并噻唑部分作为抗胃癌药物的叔酰胺衍生物。

  摘要：

  在我们先前关于抗微管蛋白和抗胃癌药物的研究的基础上，并继续进行，合成了结合苯并噻唑部分的新型叔酰胺衍生物，并在体外研究了其抗增殖活性。根据体外抗增殖活性结果探索了初步的结构活性关系（SAR）。某些化合物可以显着抑制三种癌细胞（HCT-116，MGC-803和PC-3细胞）的增殖，化合物F10对HCT-116细胞（IC 50  = 0.182μM），MGC-803细胞表现出优异的抗增殖活性（IC 50  = 0.035μM），PC-3细胞（IC 50  = 2.11μM）和SGC-7901细胞（IC50  = 0.049μM）。化合物F10有效抑制微管蛋白聚合（IC 50  = 1.9μM），并与微管蛋白的秋水仙碱结合位点结合。分子对接结果表明，化合物F10可以与β-微管蛋白的秋水仙碱结合位点紧密结合。此外，化合物F10可以调节Hippo / YAP信号通路。由于Hippo级联激活YAP，化合物F10从其最开始的MST1

  DOI：

  10.1016/j.ejmech.2020.112618

文献信息

• Synthesis and Antiproliferative Evaluation of 3-Chloroazetidin-2-ones with Antimitotic Activity: Heterocyclic Bridged Analogues of Combretastatin A-4
  作者：Azizah M. Malebari、Shu Wang、Thomas F. Greene、Niamh M. O’Boyle、Darren Fayne、Mohemmed Faraz Khan、Seema M. Nathwani、Brendan Twamley、Thomas McCabe、Daniela M. Zisterer、Mary J. Meegan

  DOI：10.3390/ph14111119

  日期：——

  development of multidrug resistance has limited their clinical activity. We report the synthesis and biological properties of a series of novel 3-chloro-β-lactams and 3,3-dichloro-β-lactams (2-azetidinones) that are structurally related to the tubulin polymerisation inhibitor and vascular targeting agent, Combretastatin A-4. These compounds were evaluated as potential tubulin polymerisation inhibitors and for

  以微管蛋白为靶点的抗有丝分裂药物是最广泛使用的化疗药物之一。然而，多重耐药性的发展限制了它们的临床活性。我们报道了一系列新型 3-氯-β-内酰胺和 3,3-二氯-β-内酰胺（2-氮杂环丁酮）的合成和生物学特性，它们在结构上与微管蛋白聚合抑制剂和血管靶向剂 Combretastatin A 相关-4。这些化合物被评估为潜在的微管蛋白聚合抑制剂及其对乳腺癌细胞的抗增殖作用。许多化合物在 MCF-7 乳腺癌细胞中显示出有效的活性，例如化合物10n (3-氯-4-(3-羟基-4-甲氧基-苯基)-1-(3,4,5-三甲氧基苯基)氮杂环丁烷-2-酮)和化合物11n (3,3-二氯-4-(3-羟基-4-甲氧基苯基)-1-(3,4,5-三甲氧基苯基)-氮杂环丁烷-2-酮)，IC 50值分别为 17 和 31 nM，并且显示出与 Combretastatin A-4 相当的细胞效应。化合物10n对非致瘤性 HEK-293T
• Design, synthesis and biological evaluation of N-benzylaryl cinnamide derivatives as tubulin polymerization inhibitors capable of promoting YAP degradation with potent anti-gastric cancer activities
  作者：Xiang-Jing Fu、Jiao Huang、Na Li、Yun-He Liu、Qiu-Ge Liu、Shuo Yuan、Yan Xu、Yi-Fan Chen、Yu-Xuan Zhao、Jian Song、Sai-Yang Zhang、Yi-Ru Bai

  DOI：10.1016/j.ejmech.2023.115883

  日期：2023.12

  apoptosis, effectively inhibit the colony formatting ability and cause morphological changes in MGC-803 and SGC-7901 cells. Compound 15e (MY-1076) exhibited significant regulatory effects on the expression levels of cell cycle and apoptosis-related proteins. Taken together, we here reported a novel N-benzylaryl cinnamide derivative 15e (MY-1076) as a tubulin polymerization inhibitor capable of promoting

  在这项工作中，我们利用 N-苄基芳基衍生物 9 作为先导化合物，并通过引入肉桂酰片段采用分子杂交策略，成功设计合成了 33 种新型 N-苄基芳基肉桂酰胺衍生物 15a∼15 ag。探索体外抗增殖活性，并对其结构-活性关系进行初步分析和总结。大多数化合物对 MGC-803 、 HCT-116 和 KYSE450 细胞表现出显着的抑制效力，IC50 值低于 0.5 μM。其中，化合物 15e （MY-1076） 对 MGC-803、SGC-7901、HCT-116 和 KYSE450 细胞的增殖抑制作用最有效，IC50 值分别为 0.019、0.017、0.020 和 0.044 μM，比秋水仙碱和先导化合物 9 更有效。此外，化合物 15e （MY-1076） 对其他 13 种类型的肿瘤细胞仍表现出显着的抑制增殖活性 （IC50 值 < 0.1 μM）。进一步研究显示，化合物 15e （MY-1076）
• Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities
  作者：Bo-Wen Wu、Wen-Jing Huang、Yun-He Liu、Qiu-Ge Liu、Jian Song、Tao Hu、Ping Chen、Sai-Yang Zhang

  DOI：10.1016/j.ejmech.2023.116118

  日期：2024.2

  esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 μM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 μM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based

  在本工作中，我们利用分子杂交策略设计并合成了新型1,2,3-三唑苯并噻唑衍生物K1-26 。探讨了其对MGC-803、Kyse30和HCT-116细胞的抗增殖活性，并初步对其构效关系进行了总结。其中，化合物K18的增殖抑制活性最强，食管癌细胞Kyse30和EC-109对其作用最敏感（IC 50值分别为0.042和0.038 μM）。化合物K18有效抑制微管蛋白聚合 (IC 50 = 0.446 μM)，从而阻碍 Kyse30 和 EC-109 细胞中微管蛋白聚合成丝状微管。此外，化合物K18通过UPS 途径诱导致癌蛋白 YAP 降解。基于这些分子水平的双重作用，化合物K18可以诱导Kyse30和EC-109细胞的G2/M期阻滞和细胞凋亡，并调节细胞周期和凋亡相关蛋白的表达水平。总之，我们的研究结果强调了一种新型的 1,2,3-三唑苯并噻唑衍生物K18 ，它具有治疗食道癌的巨大潜力。
• Synthesis and Biochemical Evaluation of 3-Phenoxy-1,4-diarylazetidin-2-ones as Tubulin-Targeting Antitumor Agents
  作者：Thomas F. Greene、Shu Wang、Lisa M. Greene、Seema M. Nathwani、Jade K. Pollock、Azizah M. Malebari、Thomas McCabe、Brendan Twamley、Niamh M. O’Boyle、Daniela M. Zisterer、Mary J. Meegan

  DOI：10.1021/acs.jmedchem.5b01086

  日期：2016.1.14

  Structure-activity relationships for a series of 3-phenoxy-1,4-diarylazetidin-2-ones were investigated, leading to the discovery of a number of potent antiproliferative compounds, including trans-4-(3-hydroxy-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (78b) and trans-4-(3-amino-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (90b). X-ray crystallography studies indicate the potential importance of the torsional angle between the 1-phenyl A ring and 4-phenyl B ring for potent antiproliferative activity and that a trans configuration between the 3-phenoxy and 4-phenyl rings is generally optimal. These compounds displayed IC50 values of 38 and 19 nM, respectively, in MCF-7 breast cancer cells, inhibited the polymerization of isolated tubulin in vitro, disrupted the microtubular structure in MCF-7 cells as visualized by confocal microscopy, and caused G(2)/M arrest and apoptosis. Compound 90b possessed a mean GI50 value of 22 nM in the NCI60 cell line screen, displayed minimal cytotoxicity, and was shown to interact at the colchicine-binding site on beta-tubulin. Phosphate and amino acid prodrugs of both 78b and 90b were synthesized, of which the alanine amide 102b retained potency and is a promising candidate for further clinical development.
• Synthesis, biochemical and molecular modelling studies of antiproliferative azetidinones causing microtubule disruption and mitotic catastrophe
  作者：Niamh M. O’Boyle、Miriam Carr、Lisa M. Greene、Niall O. Keely、Andrew J.S. Knox、Thomas McCabe、David G. Lloyd、Daniela M. Zisterer、Mary J. Meegan

  DOI：10.1016/j.ejmech.2011.07.039

  日期：2011.9

  The structure-activity relationships of antiproliferative beta-lactams, focusing on modifications at the 4-position of the beta-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC(50) value of 0.22 mu M. The mechanism of action was demonstrated to be by inhibition of tubulin polymerisation. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for combretastatin A-4 and for 26 was demonstrated in breast cancer cells for the first time, as evidenced by the formation of giant, multinucleated cells. (C) 2011 Elsevier Masson SAS. All rights reserved.