(2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4-dichlorophenyl)-2-propen-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4-dichlorophenyl)-2-propen-1-one
• 英文别名: (E)-3-(2,4-dichlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 化学式: C₁₈H₁₆Cl₂O₄
• 分子量: 367.229
• InChiKey: FSJUBEXCWNLNCS-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4-dichlorophenyl)-2-propen-1-one 在 三氟乙酸 作用下， 反应 0.33h， 以83%的产率得到3-(2,4-Dichlorophenyl)-4,5,6-trimethoxy-2,3-dihydroinden-1-one
  参考文献：
  名称：

  The synthesis of indanones related to combretastatin A-4 via microwave-assisted Nazarov cyclization of chalcones

  摘要：

  A fast and efficient microwave-assisted synthesis of combretastatin A-4-like indationes has been developed. Microwave irradiation provides a useful alternative to traditional heating techniques to promote the TFA-catalyzed Nazarov cyclization of chalcones. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.12.110
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 、 2,4-二氯苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4-dichlorophenyl)-2-propen-1-one
  参考文献：
  名称：

  作为具有抗肿瘤效力的微管蛋白聚合抑制剂的一系列新型苯并噻嗪衍生物

  摘要：

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。

  DOI：

  10.1016/j.bioorg.2020.104585

文献信息

• Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors
  作者：Lívia B. Salum、Wanessa F. Altei、Louise D. Chiaradia、Marlon N.S. Cordeiro、Rafael R. Canevarolo、Carolina P.S. Melo、Evelyn Winter、Bruno Mattei、Hikmat N. Daghestani、Maria Cláudia Santos-Silva、Tânia B. Creczynski-Pasa、Rosendo A. Yunes、José A. Yunes、Adriano D. Andricopulo、Billy W. Day、Ricardo J. Nunes、Andreas Vogt

  DOI：10.1016/j.ejmech.2013.02.037

  日期：2013.5

  Based on classical colchicine site ligands and a computational model of the colchicine binding site on beta tubulin, two classes of chalcone derivatives were designed, synthesized and evaluated for inhibition of tubulin assembly and toxicity in human cancer cell lines. Docking studies suggested that the chalcone scaffold could fit the colchicine site on tubulin in an orientation similar to that of the natural product. In particular, a 3,4,5-trimethoxyphenyl ring adjacent to the carbonyl group appeared to benefit the ligand-tubulin interaction, occupying the same subcavity as the corresponding moiety in colchicine. Consistent with modeling predictions, several 3,4,5-trimethoxychalcones showed improved cytotoxicity to murine acute lymphoblastic leukemia cells compared with a previously described parent compound, and inhibited tubulin assembly in vitro as potently as colchicine. The most potent chalcones inhibited the growth of human leukemia cell lines at nanomolar concentrations, caused microtubule destabilization and mitotic arrest in human cervical cancer cells, and inhibited human breast cancer cell migration in scratch wound and Boyden chamber assays. (C) 2013 Elsevier Masson SAS. All rights reserved.
• A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency
  作者：Bin Wang、Li-Ren Wang、Lu-Lu Liu、Wei Wang、Ruo-Jun Man、Da-Jun Zheng、Yu-Shan Deng、Yu-Shun Yang、Chen Xu、Hai-Liang Zhu

  DOI：10.1016/j.bioorg.2020.104585

  日期：2021.3

  In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker for CA-4 modification for the first time. Among them, the hit compound D8 showed potential on inhibiting the growth of several cancer cell lines (IC50

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。
• The synthesis of indanones related to combretastatin A-4 via microwave-assisted Nazarov cyclization of chalcones
  作者：Nicholas J. Lawrence、E. Simon M. Armitage、Benjamin Greedy、Darren Cook、Sylvie Ducki、Alan T. McGown

  DOI：10.1016/j.tetlet.2005.12.110

  日期：2006.3

  A fast and efficient microwave-assisted synthesis of combretastatin A-4-like indationes has been developed. Microwave irradiation provides a useful alternative to traditional heating techniques to promote the TFA-catalyzed Nazarov cyclization of chalcones. (c) 2006 Elsevier Ltd. All rights reserved.