1-(3-chloro-4-methoxyphenyl)-4-(4-nitrophenyl)butane-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-chloro-4-methoxyphenyl)-4-(4-nitrophenyl)butane-1-one
• 英文别名: 1-(3-Chloro-4-methoxyphenyl)-4-(4-nitrophenyl)butan-1-one
• 化学式: C₁₇H₁₆ClNO₄
• 分子量: 333.771
• InChiKey: AASXVIZHUSWXJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-4-methoxyphenyl)-4-(4-nitrophenyl)butane-1-one 、 乙酸酐 在 四甲基乙二胺 作用下， 生成 1-(3-chloro-4-methoxyphenyl)-2-methylene-4-(4-nitrophenyl)butane-1-one
  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：

  4-(4-硝基苯基)丁酰氯 、 2-氯苯甲醚 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以92%的产率得到1-(3-chloro-4-methoxyphenyl)-4-(4-nitrophenyl)butane-1-one
  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

• 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.