2-(3,4-dimethoxyphenyl)-5-nitrobenzofuran

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: 2-(3,4-dimethoxyphenyl)-5-nitrobenzofuran
• 英文别名: 2-(3,4-Dimethoxyphenyl)-5-nitro-1-benzofuran；2-(3,4-dimethoxyphenyl)-5-nitro-1-benzofuran
• 化学式: C₁₆H₁₃NO₅
• 分子量: 299.283
• InChiKey: WMSRXVPREIBEAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-5-nitrobenzofuran 在 palladium on activated charcoal 、 氢气 、 三溴化硼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 4-(5-aminobenzofuran-2-yl)benzene-1,2-diol
  参考文献：
  名称：

  Design and synthesis of 2-phenylnaphthalenoids and 2-phenylbenzofuranoids as DNA topoisomerase inhibitors and antitumor agents

  摘要：

  Eight 2-phenylnaphthalenoids (2PNs) (3a h) and twenty four 2-phenylbenzofuranoids (2PBF5) (4a-4j, 5a-5j, 6a, 6f-6h) were successfully designed, synthesized and their antiproliferative and in vitro DNA topoisomerase inhibitory activities were evaluated. Nine compounds (four 2PNs and five 2PBFs) showed either Topol or TopoII alpha inhibitory activities. Six compounds (four 2PNs and two 2PBFs) exhibited potent cytotoxicity with IC50 values for 72 h exposure ranging from 0.3 to above 20 mu M against MDA-MB-231, MDA-MB-435, HepG2 and PC3 cell lines. The two 2PBFs displayed comparable and even better antiproliferative as well as TopoII alpha inhibitory activities than 2PNs. Interestingly, the active 2PBFs displayed different mechanisms of TopoII alpha inhibition from that of 2PNs, suggesting that the chromophore scaffold replacement may result in a change of the binding site of inhibitors to TopoII alpha. Furthermore, the mechanisms of antiproliferation on MDA-MB-231 cells indicate that compounds 5a and 5f are promising for further development of anticancer agents. The results of this study reveal that the evolutionary strategy of medicinal chemistry through scaffold hopping is a promising strategy for structure optimization of TopoII alpha inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.07.048
• 作为产物：
  描述：

  2-羟基-5-硝基苄醇 在 三乙胺 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 4.0h， 生成 2-(3,4-dimethoxyphenyl)-5-nitrobenzofuran
  参考文献：
  名称：

  硝基-和甲氧基-2-苯基苯并呋喃作为人单胺氧化酶抑制剂的合成和体外研究

  摘要：

  设计并合成了一系列新的 2-苯基苯并呋喃衍生物，以确定 MAO 抑制活性和选择性的相关结构特征。在 2-苯环中引入了甲氧基取代基，而苯并呋喃部分未被取代或在 5 或 7 位被硝基取代。苯环和苯并呋喃部分的取代模式决定了对 MAO-A 或 MAO-B 的亲和力。2-(3-甲氧基苯基)-5-硝基苯并呋喃9是该系列中最有效的 MAO-B 抑制剂 (IC 50  = 0.024 µM)，而 7-硝基-2-苯基苯并呋喃7是最有效的 MAO-A 抑制剂(IC 50 = 0.168 µM)，两者都作为可逆抑制剂。2-苯环上甲氧基的数量和位置对抑制活性有重要影响。分子对接研究证实了实验结果，并强调了关键残基在酶抑制中的重要性。

  DOI：

  10.1016/j.bioorg.2020.104616

文献信息

• Design and synthesis of 2-phenylnaphthalenoids and 2-phenylbenzofuranoids as DNA topoisomerase inhibitors and antitumor agents
  作者：Huilin Hao、Wang Chen、Jing Zhu、Chunhua Lu、Yuemao Shen

  DOI：10.1016/j.ejmech.2015.07.048

  日期：2015.9

  Eight 2-phenylnaphthalenoids (2PNs) (3a h) and twenty four 2-phenylbenzofuranoids (2PBF5) (4a-4j, 5a-5j, 6a, 6f-6h) were successfully designed, synthesized and their antiproliferative and in vitro DNA topoisomerase inhibitory activities were evaluated. Nine compounds (four 2PNs and five 2PBFs) showed either Topol or TopoII alpha inhibitory activities. Six compounds (four 2PNs and two 2PBFs) exhibited potent cytotoxicity with IC50 values for 72 h exposure ranging from 0.3 to above 20 mu M against MDA-MB-231, MDA-MB-435, HepG2 and PC3 cell lines. The two 2PBFs displayed comparable and even better antiproliferative as well as TopoII alpha inhibitory activities than 2PNs. Interestingly, the active 2PBFs displayed different mechanisms of TopoII alpha inhibition from that of 2PNs, suggesting that the chromophore scaffold replacement may result in a change of the binding site of inhibitors to TopoII alpha. Furthermore, the mechanisms of antiproliferation on MDA-MB-231 cells indicate that compounds 5a and 5f are promising for further development of anticancer agents. The results of this study reveal that the evolutionary strategy of medicinal chemistry through scaffold hopping is a promising strategy for structure optimization of TopoII alpha inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis and in vitro study of nitro- and methoxy-2-phenylbenzofurans as human monoamine oxidase inhibitors
  作者：Giovanna L. Delogu、Amit Kumar、Gianluca Gatto、Fernando Bustelo、Lucía M. Saavedra、Maria Isabel Rodríguez-Franco、Reyes Laguna、Dolores Viña

  DOI：10.1016/j.bioorg.2020.104616

  日期：2021.2

  A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran

  设计并合成了一系列新的 2-苯基苯并呋喃衍生物，以确定 MAO 抑制活性和选择性的相关结构特征。在 2-苯环中引入了甲氧基取代基，而苯并呋喃部分未被取代或在 5 或 7 位被硝基取代。苯环和苯并呋喃部分的取代模式决定了对 MAO-A 或 MAO-B 的亲和力。2-(3-甲氧基苯基)-5-硝基苯并呋喃9是该系列中最有效的 MAO-B 抑制剂 (IC 50  = 0.024 µM)，而 7-硝基-2-苯基苯并呋喃7是最有效的 MAO-A 抑制剂(IC 50 = 0.168 µM)，两者都作为可逆抑制剂。2-苯环上甲氧基的数量和位置对抑制活性有重要影响。分子对接研究证实了实验结果，并强调了关键残基在酶抑制中的重要性。