2′,4′,6′-三乙氧基苯乙酮 | 480439-37-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2′,4′,6′-三乙氧基苯乙酮
• 英文名称: 1-(2,4,6-triethoxy-phenyl)-ethanone
• 英文别名: 1-(2,4,6-Triaethoxy-phenyl)-aethanon；2',4',6'-Triethoxyacetophenone；1-(2,4,6-triethoxyphenyl)ethanone
• CAS: 480439-37-0
• 化学式: C₁₄H₂₀O₄
• 分子量: 252.31
• InChiKey: UUHSEANPLSBYIC-UHFFFAOYSA-N

物化性质

• 熔点：
  70-74 °C(lit.)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  2,4,6-三乙氧基苯甲醛 、 2′,4′,6′-三乙氧基苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以21%的产率得到2,2',4,4',6,6'-hexaethoxychalcone
  参考文献：
  名称：

  Investigation of Chalcones as Selective Inhibitors of the Breast Cancer Resistance Protein: Critical Role of Methoxylation in both Inhibition Potency and Cytotoxicity

  摘要：

  ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogues (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. Six compounds producing complete inhibition with IC50 values below 0.5 mu M and high selectivity for ABCG2 were identified. The number and position of methoxy substituents appeared to be critical for both inhibition and cytotoxicity. The best compounds, with potent inhibition and low toxicity, contained an N-methyl-1-indolyl (compound 38) or a 6'-hydroxyl-2',4'-dimethoxy-1-phenyl (compound 27) moiety (A-ring) and two methoxy groups at positions 2 and 6 of the 3-phenyl moiety (B-ring). Methoxy substitution contributed to inhibition at positions 3 and 5, but had a negative effect at position 4. Finally, methoxy groups at positions 3, 4, and 5 of the B-ring markedly increased cytotoxicity and, therefore, should be avoided.

  DOI：

  10.1021/jm2016528
• 作为产物：
  描述：

  间苯三酚 在 三氟化硼乙醚 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2′,4′,6′-三乙氧基苯乙酮
  参考文献：
  名称：

  基于Uvaretin全合成中间体的小型文库构建与生物学评价

  摘要：

  发现治疗剂：新的生物活性剂，无论是单独的还是组合的，都是通过合成操纵 uvaretin 类天然产物的全合成过程中的中间体而构建的。发现增加酚核心的疏水特性与降低单一试剂的细胞毒性相关。本文展示了由我们的 uvaretin 类天然产物的全合成路线的中间体构建的新的小型化学筛选库 (CSL) 的合成。组装了许多在查尔酮核内的酚基上具有各种取代的基于查尔酮的 CSL。通过细胞毒性研究，发现查耳酮酚核心的疏水性水平存在偏差：具有更多疏水核心的细胞毒性较小。此外，据观察，在胰腺癌细胞系 MIA PaCa-2 中用 6-硫嘌呤评估的增强作用可通过在酚核心上包含较少疏水性特征来调节。的作用存在于 uvaretin 家族中的邻羟基苄基被证明具有细胞毒性。合并在这项工作中构建的 CSL 上进行的所有构效关系研究导致构建了一种新的查尔酮杂化物，该杂化物同时具有细胞毒性烯酮基团和小分子增强的还原烯酮基团。

  DOI：

  10.1002/cmdc.202001010

文献信息

• Antimitotic and Antiproliferative Activities of Chalcones: Forward Structure–Activity Relationship
  作者：Ahcène Boumendjel、Julien Boccard、Pierre-Alain Carrupt、Edwige Nicolle、Madeleine Blanc、Annabelle Geze、Luc Choisnard、Denis Wouessidjewe、Eva-Laure Matera、Charles Dumontet

  DOI：10.1021/jm0708331

  日期：2008.4.1

  A series of 59 chalcones was prepared and evaluated for the antimitotic effect against K562 leukemia cells. The most active chalcones were evaluated for their antiproliferative activity against a panel of I I human and murine cell cancer lines. We found that three chalcones were of great interest as potential antimitotic drugs. In vivo safety studies conducted on one of the most active chalcones revealed that the compound was safe, allowing further in vivo antitumor evaluation.
• Acupuncture for the Treatment of Cocaine Addiction
  作者：V. Ginzburg

  DOI：10.1001/jama.287.14.1800

  日期：2002.4.10
• Investigation of Chalcones as Selective Inhibitors of the Breast Cancer Resistance Protein: Critical Role of Methoxylation in both Inhibition Potency and Cytotoxicity
  作者：Glaucio Valdameri、Charlotte Gauthier、Raphaël Terreux、Rémy Kachadourian、Brian J. Day、Sheila M. B. Winnischofer、Maria E. M. Rocha、Véronique Frachet、Xavier Ronot、Attilio Di Pietro、Ahcène Boumendjel

  DOI：10.1021/jm2016528

  日期：2012.4.12

  ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogues (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. Six compounds producing complete inhibition with IC50 values below 0.5 mu M and high selectivity for ABCG2 were identified. The number and position of methoxy substituents appeared to be critical for both inhibition and cytotoxicity. The best compounds, with potent inhibition and low toxicity, contained an N-methyl-1-indolyl (compound 38) or a 6'-hydroxyl-2',4'-dimethoxy-1-phenyl (compound 27) moiety (A-ring) and two methoxy groups at positions 2 and 6 of the 3-phenyl moiety (B-ring). Methoxy substitution contributed to inhibition at positions 3 and 5, but had a negative effect at position 4. Finally, methoxy groups at positions 3, 4, and 5 of the B-ring markedly increased cytotoxicity and, therefore, should be avoided.
• Construction and Biological Evaluation of Small Libraries Based on the Intermediates within the Total Synthesis of Uvaretin
  作者：Shashika Perera、Asantha Fernando、Johnathan Dallman、Chamitha Weeramange、Ashabha Lansakara、Thi Nguyen、Ryan J. Rafferty

  DOI：10.1002/cmdc.202001010

  日期：2021.5.18

  therapeutic agents: New bioactive agents, either as sole or combinational agents, have been constructed through the synthetic manipulation of the intermediates within the total synthesis of the uvaretin class of natural products. It was found that increasing the hydrophobic character of the phenolic core correlates to a decrease in sole agent cytotoxicity. The synthesis of new, small chemical screening libraries

  发现治疗剂：新的生物活性剂，无论是单独的还是组合的，都是通过合成操纵 uvaretin 类天然产物的全合成过程中的中间体而构建的。发现增加酚核心的疏水特性与降低单一试剂的细胞毒性相关。本文展示了由我们的 uvaretin 类天然产物的全合成路线的中间体构建的新的小型化学筛选库 (CSL) 的合成。组装了许多在查尔酮核内的酚基上具有各种取代的基于查尔酮的 CSL。通过细胞毒性研究，发现查耳酮酚核心的疏水性水平存在偏差：具有更多疏水核心的细胞毒性较小。此外，据观察，在胰腺癌细胞系 MIA PaCa-2 中用 6-硫嘌呤评估的增强作用可通过在酚核心上包含较少疏水性特征来调节。的作用存在于 uvaretin 家族中的邻羟基苄基被证明具有细胞毒性。合并在这项工作中构建的 CSL 上进行的所有构效关系研究导致构建了一种新的查尔酮杂化物，该杂化物同时具有细胞毒性烯酮基团和小分子增强的还原烯酮基团。