ethyl (3-methyl-4-propionylphenoxy)acetate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl (3-methyl-4-propionylphenoxy)acetate
• 英文别名: Ethyl 2-(3-methyl-4-propanoylphenoxy)acetate
• 化学式: C₁₄H₁₈O₄
• 分子量: 250.295
• InChiKey: CTNWGAIJDRZWEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 ethyl (3-methyl-4-propionylphenoxy)acetate 在 四甲基甲烷二胺 作用下， 反应 85.0h， 以14%的产率得到ethyl (3-methyl-4-(2-methylacryloyl)phenoxy)acetate
  参考文献：
  名称：

  A New Lead for Nonpeptidic Active-Site-Directed Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus Main Protease Discovered by a Combination of Screening and Docking Methods

  摘要：

  The coronavirus main protease, M-pro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M-pro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M-pro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K-i value of 35.3 mu M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

  DOI：

  10.1021/jm0501782
• 作为产物：
  描述：

  间甲基苯甲醚 在 三氯化铝 、 potassium tert-butylate 、 potassium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 ethyl (3-methyl-4-propionylphenoxy)acetate
  参考文献：
  名称：

  A New Lead for Nonpeptidic Active-Site-Directed Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus Main Protease Discovered by a Combination of Screening and Docking Methods

  摘要：

  The coronavirus main protease, M-pro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M-pro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M-pro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K-i value of 35.3 mu M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

  DOI：

  10.1021/jm0501782

文献信息

• Inhibitory effects of ethacrynic acid analogues lacking the α,β-unsaturated carbonyl unit and para-acylated phenols on human cancer cells
  作者：Zack E. Bryant、Romy F.J. Janser、Medina Jabarkhail、Melissa S. Candelaria-Lyons、Brittni B. Romero、Severine Van slambrouck、Wim F.A. Steelant、Ingo Janser

  DOI：10.1016/j.bmcl.2010.12.074

  日期：2011.2

  A series of ethacrynic acid analogues, lacking the alpha,beta-unsaturated carbonyl unit, was synthesized and subsequently evaluated for their ability to inhibit the migration of human breast cancer cells, Hs578Ts(i) 8 as well as of human prostate cancer cells, C4-2B. These cell lines provide a good model system to study migration and invasion, since they represent metastatic cancer. Our studies show that ethacrynic acid analogues with methyl substituents at the aromatic ring demonstrate no inhibitory effect on the migration of both cancer cell lines, whereas a precursor in the synthesis of these ethacrynic acid analogues (II-1, a para-acylated m-cresol) is an excellent inhibitor of the migration of both cancer cell lines. (C) 2010 Elsevier Ltd. All rights reserved.
• A New Lead for Nonpeptidic Active-Site-Directed Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus Main Protease Discovered by a Combination of Screening and Docking Methods
  作者：Ulrich Kaeppler、Nikolaus Stiefl、Markus Schiller、Radim Vicik、Alexander Breuning、Werner Schmitz、Daniel Rupprecht、Carsten Schmuck、Knut Baumann、John Ziebuhr、Tanja Schirmeister

  DOI：10.1021/jm0501782

  日期：2005.11.1

  The coronavirus main protease, M-pro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M-pro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M-pro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K-i value of 35.3 mu M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.