ethyl (4-butyryl-2-chlorophenoxy)acetate | 868075-00-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl (4-butyryl-2-chlorophenoxy)acetate
• 英文别名: Ethyl 2-(4-butanoyl-2-chlorophenoxy)acetate
• CAS: 868075-00-7
• 化学式: C₁₄H₁₇ClO₄
• 分子量: 284.74
• InChiKey: MEXBCFJXEKNYCY-UHFFFAOYSA-N

物化性质

• 熔点：
  97-98 °C(Solv: ethanol (64-17-5))
• 沸点：
  399.8±32.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  8
• 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：

  ethyl (4-butyryl-2-chlorophenoxy)acetate 、 乙酸酐 在 四甲基乙二胺 作用下， 反应 85.0h， 以33%的产率得到ethyl (2-chloro-4-(2-methylenebutyryl)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：

  2-氯苯甲醚 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 (4-butyryl-2-chlorophenoxy)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

• Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid
  作者：Marie-Adrienne Dude、Ulrich Kaeppler、Monika Herb、Markus Schiller、Franziska Schulz、Birgit Vedder、Saskia Heppner、Gabriele Pradel、Jiri Gut、Philip Rosenthal、Tanja Schirmeister、Matthias Leippe、Christoph Gelhaus

  DOI：10.3390/molecules14010019

  日期：——

  A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC50 values of 9.0 and 18.8 μM against Plasmodia.

  一系列依他尼酸衍生物被合成并筛选其对恶性疟原虫的体外活性，以及它们对重组表达的法西平-2和法西平-3的活性。该系列中活性最强的两种化合物对疟原虫的IC50值分别为9.0和18.8 μM。
• 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.