3-ethyl-4,5-dihydrobenzo<1,2-b>furan-4,5-dione

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-ethyl-4,5-dihydrobenzo<1,2-b>furan-4,5-dione
• 英文别名: 3-Ethyl-1-benzofuran-4,5-dione
• 化学式: C₁₀H₈O₃
• 分子量: 176.172
• InChiKey: PEQQAADSPBELLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-二甲基-1,3-丁二烯 、 3-ethyl-4,5-dihydrobenzo<1,2-b>furan-4,5-dione 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 水 、 甲苯 为溶剂， 反应 3.0h， 生成 3-ethyl-7,8-dimethylnaphtho[1,2-b]furan-4,5-dione
  参考文献：
  名称：

  Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

  摘要：

  In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b] furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control beta-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H... pi interactions with Trp105 and Phe178 residues compared to the control beta-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.004
• 作为产物：
  描述：

  3-ethyl-5-benzofuranol 在 2-碘酰基苯甲酸 作用下， 以 水 为溶剂， 生成 3-ethyl-4,5-dihydrobenzo<1,2-b>furan-4,5-dione
  参考文献：
  名称：

  Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

  摘要：

  In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b] furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control beta-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H... pi interactions with Trp105 and Phe178 residues compared to the control beta-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.004

文献信息

• 2-Ethoxybut-2-enal N,N-dimethylhydrazone: A useful reagent for the synthesis of furo[2,3-f]quinoline-4,5-diones
  作者：Pascal Nebois、Omar Cherkaoui、Leila Benameur、Houda Fillion、Bernard Fenet

  DOI：10.1016/s0040-4020(01)85566-6

  日期：1994.1

  Regiospecific synthesis of substituted furo[2,3-f]quinoline-4,5-diones were performed using 2-ethoxybut-2-enal N,N-dimethylhydrazone as a nucl

  使用2-乙氧基丁-2-烯醛N，N-二甲基hydr作为核素进行取代呋喃[2,3 - f ]喹啉-4,5-二酮的区域特异性合成
• Nebois Pascal, Cherkaoui Omar, Benameur Leila, Fillion Houda, Fenet Berna+, Tetrahedron, 50 (1994) N 28, S 8457-8464
  作者：Nebois Pascal, Cherkaoui Omar, Benameur Leila, Fillion Houda, Fenet Berna+

  DOI：——

  日期：——
• Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile
  作者：Jinlei Bian、Xiang Li、Nan Wang、Xingsen Wu、Qidong You、Xiaojin Zhang

  DOI：10.1016/j.ejmech.2017.02.004

  日期：2017.3

  In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b] furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control beta-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H... pi interactions with Trp105 and Phe178 residues compared to the control beta-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.