2-((4-(((3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)isoindoline-1,3-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-((4-(((3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)isoindoline-1,3-dione
• 英文别名: 2-[[4-[[(3-Bromo-1,4-dioxonaphthalen-2-yl)amino]methyl]triazol-1-yl]methyl]isoindole-1,3-dione；2-[[4-[[(3-bromo-1,4-dioxonaphthalen-2-yl)amino]methyl]triazol-1-yl]methyl]isoindole-1,3-dione
• 化学式: C₂₂H₁₄BrN₅O₄
• 分子量: 492.288
• InChiKey: XCMQALJSZGPWDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,3-二溴-1,4-萘醌 在 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.0h， 生成 2-((4-(((3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety

  摘要：

  In our continued search for novel trypanocidal compounds, twenty-six derivatives of para-and orthonaphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 mu M. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 mu M for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.055

文献信息

• Searching Anti-Zika Virus Activity in 1H-1,2,3-Triazole Based Compounds
  作者：Willyenne M. Dantas、Valentina N. M. de Oliveira、Diogo A. L. Santos、Gustavo Seabra、Prem P. Sharma、Brijesh Rathi、Lindomar J. Pena、Ronaldo N. de Oliveira

  DOI：10.3390/molecules26195869

  日期：——

  Zika virus (ZIKV) is a mosquito-borne virus belonging to the Flaviviridae family and is responsible for an exanthematous disease and severe neurological manifestations, such as microcephaly and Guillain-Barré syndrome. ZIKV has a single strand positive-sense RNA genome that is translated into structural and non-structural (NS) proteins. Although it has become endemic in most parts of the tropical world, Zika still does not have a specific treatment. Thus, in this work we evaluate the cytotoxicity and antiviral activities of 14 hybrid compounds formed by 1H-1,2,3-triazole, naphthoquinone and phthalimide groups. Most compounds showed low cytotoxicity to epithelial cells, specially the 3b compound. After screening with all compounds, 4b was the most active against ZIKV in the post-infection test, obtaining a 50% inhibition concentration (IC50) of 146.0 µM and SI of 2.3. There were no significant results for the pre-treatment test. According to the molecular docking compound, 4b was suggested with significant binding affinity for the NS5 RdRp protein target, which was further corroborated by molecular dynamic simulation studies.

  寨卡病毒（ZIKV）是一种蚊媒病毒，属于黄病毒科，负责引发皮疹性疾病和严重的神经系统症状，如小头畸形和吉兰-巴雷综合征。ZIKV具有单链正义RNA基因组，可翻译成结构和非结构（NS）蛋白质。尽管在热带世界的大部分地区已成为地方性疾病，但寨卡病毒仍没有特定的治疗方法。因此，在这项研究中，我们评估了由1H-1,2,3-三唑、萘醌和邻苯二甲酰亚胺基团组成的14种混合化合物的细胞毒性和抗病毒活性。大多数化合物对上皮细胞显示出较低的细胞毒性，特别是3b化合物。在对所有化合物进行筛选后，4b在后感染测试中对ZIKV表现出最强活性，获得了146.0 µM的50%抑制浓度（IC50）和2.3的SI。预处理测试没有显著结果。根据分子对接化合物，4b被建议具有与NS5 RdRp蛋白靶点的显著结合亲和力，这一结果进一步得到了分子动力学模拟研究的证实。
• Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety
  作者：Emilay B.T. Diogo、Gleiston G. Dias、Bernardo L. Rodrigues、Tiago T. Guimarães、Wagner O. Valença、Celso A. Camara、Ronaldo N. de Oliveira、Mauro G. da Silva、Vitor F. Ferreira、Yen Galdino de Paiva、Marilia O.F. Goulart、Rubem F.S. Menna-Barreto、Solange L. de Castro、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.bmc.2013.08.055

  日期：2013.11

  In our continued search for novel trypanocidal compounds, twenty-six derivatives of para-and orthonaphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 mu M. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 mu M for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. (C) 2013 Elsevier Ltd. All rights reserved.