2-(4-benzylpiperazine-1-carbonyl)-3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 2-(4-benzylpiperazine-1-carbonyl)-3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione
• 英文别名: 2-(4-Benzylpiperazine-1-carbonyl)-3,7,8-trimethylbenzo[g][1]benzofuran-4,5-dione；2-(4-benzylpiperazine-1-carbonyl)-3,7,8-trimethylbenzo[g][1]benzofuran-4,5-dione
• 化学式: C₂₇H₂₆N₂O₄
• 分子量: 442.514
• InChiKey: LUCVOLYBWQUGEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-benzylpiperazine-1-carbonyl)-3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione 在 NAD(P)H:quinone oxidoreductase 、 还原型辅酶II(NADPH)四钠盐 、 bovine serum albumin 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  2-Substituted 3,7,8-trimethylnaphtho[1,2- b ]furan-4,5-diones as specific L-shaped NQO1-mediated redox modulators for the treatment of non-small cell lung cancer

  摘要：

  Based on the scaffold of 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione, a series of L-shaped derivatives with substituted side chains at the position of C2 were designed by analyzing the binding mode with NQO1. The drug-like compound 6q (named as DDO-7178) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by one-electron oxidoreductases CPR (NQO1/CPR = 20.8). In addition, compound 6q showed much improved physicochemical properties such as water solubility than the control beta-lap. The follow-up studies indicated that 6q showed a NQO1-expressing cancer-cell-selective killing property. Preliminary mechanism studies on the anticancer effect indicated that 6q induced ROS production in an NQO1 dependent manner and activated Akt/MAPK pathways in a ROS-dependent fashion, thereby inducing apoptosis. In addition, emphasized compound 6q showed more significant antitumor efficacy than beta-lap without producing obvious toxic effects in vivo, which gave us a new tool for further investigation of NQO1-mediated redox modulators as anticancer drugs for the treatment of NQO1-overexpressed NSCLC. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.06.028
• 作为产物：
  描述：

  4,5-dihydro-3-methylbenzo[1,2-b]furan-4,5-dione 在 sodium chlorite 、 双氧水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 三氯氧磷 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 22.5h， 生成 2-(4-benzylpiperazine-1-carbonyl)-3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione
  参考文献：
  名称：

  2-Substituted 3,7,8-trimethylnaphtho[1,2- b ]furan-4,5-diones as specific L-shaped NQO1-mediated redox modulators for the treatment of non-small cell lung cancer

  摘要：

  Based on the scaffold of 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione, a series of L-shaped derivatives with substituted side chains at the position of C2 were designed by analyzing the binding mode with NQO1. The drug-like compound 6q (named as DDO-7178) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by one-electron oxidoreductases CPR (NQO1/CPR = 20.8). In addition, compound 6q showed much improved physicochemical properties such as water solubility than the control beta-lap. The follow-up studies indicated that 6q showed a NQO1-expressing cancer-cell-selective killing property. Preliminary mechanism studies on the anticancer effect indicated that 6q induced ROS production in an NQO1 dependent manner and activated Akt/MAPK pathways in a ROS-dependent fashion, thereby inducing apoptosis. In addition, emphasized compound 6q showed more significant antitumor efficacy than beta-lap without producing obvious toxic effects in vivo, which gave us a new tool for further investigation of NQO1-mediated redox modulators as anticancer drugs for the treatment of NQO1-overexpressed NSCLC. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.06.028

文献信息

• 2-Substituted 3,7,8-trimethylnaphtho[1,2- b ]furan-4,5-diones as specific L-shaped NQO1-mediated redox modulators for the treatment of non-small cell lung cancer
  作者：Xiaojin Zhang、Jinlei Bian、Xiang Li、Xingsen Wu、Yanan Dong、Qidong You

  DOI：10.1016/j.ejmech.2017.06.028

  日期：2017.9

  Based on the scaffold of 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione, a series of L-shaped derivatives with substituted side chains at the position of C2 were designed by analyzing the binding mode with NQO1. The drug-like compound 6q (named as DDO-7178) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by one-electron oxidoreductases CPR (NQO1/CPR = 20.8). In addition, compound 6q showed much improved physicochemical properties such as water solubility than the control beta-lap. The follow-up studies indicated that 6q showed a NQO1-expressing cancer-cell-selective killing property. Preliminary mechanism studies on the anticancer effect indicated that 6q induced ROS production in an NQO1 dependent manner and activated Akt/MAPK pathways in a ROS-dependent fashion, thereby inducing apoptosis. In addition, emphasized compound 6q showed more significant antitumor efficacy than beta-lap without producing obvious toxic effects in vivo, which gave us a new tool for further investigation of NQO1-mediated redox modulators as anticancer drugs for the treatment of NQO1-overexpressed NSCLC. (C) 2017 Published by Elsevier Masson SAS.