5-trifluoromethoxy-1H-indole-2,3-dione 3-(N-ethylthiosemicarbazone) | 1084892-95-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-trifluoromethoxy-1H-indole-2,3-dione 3-(N-ethylthiosemicarbazone)
• 英文别名: 5-trifluoromethoxy-1H-indole-2,3-dione-3-(N-ethylthiosemicarbazone)；1-ethyl-3-[[2-oxo-5-(trifluoromethoxy)indol-3-yl]amino]thiourea
• CAS: 1084892-95-4；1043565-66-7
• 化学式: C₁₂H₁₁F₃N₄O₂S
• 分子量: 332.306
• InChiKey: FJJGBQYJZRJLOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  74.75
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  氯乙酸 、 5-trifluoromethoxy-1H-indole-2,3-dione 3-(N-ethylthiosemicarbazone) 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以69%的产率得到(Z)-2-(((E)-5-trifluoromethoxy-2-oxoindolin-3-ylidene)hydrazineylidene)-3-ethyl thiazolidin-4-one
  参考文献：
  名称：

  作为具有潜在抗癌活性的 CDK2 抑制剂的 2-吲哚啉酮和噻唑啉酮支架的新型氮杂连接杂化物：计算机设计、合成、生物、分子动力学和结合自由能研究

  摘要：

  2-吲哚啉酮-噻唑烷酮的分子杂化物是一种众所周知的支架，具有多种生物活性，包括抗癌活性。因此，在基于结构的分子建模研究的当前工作中，设计和合成了一个新的 26 个杂化物库4(az) 。CDK2（关键检查点酶之一）活性位点的对接研究表明，设计分子的结合分数与参考酶的抑制剂舒尼替尼、尼达尼布和塞马卡尼相当。考虑到阿霉素，这些分子对人肝脏 (HepG2)、乳腺 (MCF7) 和结肠 (HCT-29) 细胞系显示出不同的抗增殖活性作为参考药。与对正常成纤维细胞 (WI-38) 的细胞毒活性相比，测试分子对癌细胞具有更好的选择性，以它们的选择性指数 (SI) 表示，比多柔巴星和化合物 4i是最安全的化合物。化合物4f、4g、4h和4w的 CDK2 抑制结果显示 IC 50分别为 59.43、143.6、27.42 和 61.63 nM，而舒尼替尼为 23.8 nM。为了阐明获得的这些分子的生物活性，

  DOI：

  10.1016/j.bioorg.2022.105884
• 作为产物：
  描述：

  4-乙基-3-硫代氨基脲 、 4-(三氟甲氧基)-靛红 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以67%的产率得到5-trifluoromethoxy-1H-indole-2,3-dione 3-(N-ethylthiosemicarbazone)
  参考文献：
  名称：

  Three novel compounds of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone: Synthesis, crystal structures and molecular interactions

  摘要：

  5-Trifluoromethoxy-1H-indole-2,3-dione 3-(N-ethyl/benzylthiosemicarbazone) (2a/2b) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-(N-ethylthiosemicarbazone) (3a) were synthesized. The structures of the compounds were confirmed by elemental analysis, spectral data and X-ray single crystal diffraction analysis. The morpholin ring which adopts chair conformation and ethylamino group of 3a are disordered over two sets of sites with unequal occupancy. The indole heterocycle is nearly planar and the dihedral angle between the pyrrole and the adjacent phenyl ring is 2.09 degrees (in 2a), 4.61 degrees (in 2b) and 2.16 degrees (in 3a). In all three crystal structures, a strong N-H center dot center dot center dot O hydrogen bond links the flat conjugated H-N-N=C-C=O fragment into a six-membered ring. The molecules 2a, 2b and 3a have potential groups of proton donors (thiosemicarbazone group) available for hydrogen bonding. The structures 2b and 3a consist of isolated molecules, while that of 2a contains dimers formed by C-H center dot center dot center dot O hydrogen bonds. The molecules are linked into three dimensional framework structure by a combination of mainly N-H center dot center dot center dot N and N-H center dot center dot center dot O hydrogen bonds and weak C-F center dot center dot center dot pi and pi center dot center dot center dot pi interactions. (c) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2013.06.039

文献信息

• Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives
  作者：Özlen Güzel、Nilgün Karalı、Aydın Salman

  DOI：10.1016/j.bmc.2008.08.050

  日期：2008.10

  New series of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 3a-t, 1-methyl-5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 4a-y and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones 5a-m were synthesized. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis. The new 5-methyl/trifluoromethoxy-1H-indole-2,3-dione derivatives, along with previously synthesized 5-methyl-1H-indole-2,3-dione 3-thiosemicarbazones 6a-1, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. 5-Methyl-1H-indole-2,3-dione 3-thiosemicarbazones (3b, 3d, 3f, 6c, 6d, and 6f), 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones (3q-s) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones (5e and 5j-1) were found to be the most potent inhibitors of M. tuberculosis growth described in this study. (C) 2008 Elsevier Ltd. All rights reserved.
• Three novel compounds of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone: Synthesis, crystal structures and molecular interactions
  作者：Filiz Betül Kaynak、Süheyla Özbey、Nilgün Karalı

  DOI：10.1016/j.molstruc.2013.06.039

  日期：2013.10

  5-Trifluoromethoxy-1H-indole-2,3-dione 3-(N-ethyl/benzylthiosemicarbazone) (2a/2b) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-(N-ethylthiosemicarbazone) (3a) were synthesized. The structures of the compounds were confirmed by elemental analysis, spectral data and X-ray single crystal diffraction analysis. The morpholin ring which adopts chair conformation and ethylamino group of 3a are disordered over two sets of sites with unequal occupancy. The indole heterocycle is nearly planar and the dihedral angle between the pyrrole and the adjacent phenyl ring is 2.09 degrees (in 2a), 4.61 degrees (in 2b) and 2.16 degrees (in 3a). In all three crystal structures, a strong N-H center dot center dot center dot O hydrogen bond links the flat conjugated H-N-N=C-C=O fragment into a six-membered ring. The molecules 2a, 2b and 3a have potential groups of proton donors (thiosemicarbazone group) available for hydrogen bonding. The structures 2b and 3a consist of isolated molecules, while that of 2a contains dimers formed by C-H center dot center dot center dot O hydrogen bonds. The molecules are linked into three dimensional framework structure by a combination of mainly N-H center dot center dot center dot N and N-H center dot center dot center dot O hydrogen bonds and weak C-F center dot center dot center dot pi and pi center dot center dot center dot pi interactions. (c) 2013 Elsevier B.V. All rights reserved.
• Novel Azine Linked Hybrids of 2-Indolinone and Thiazolodinone Scaffolds as CDK2 Inhibitors with Potential Anticancer Activity: In Silico Design, Synthesis, Biological, Molecular Dynamics and Binding Free Energy Studies
  作者：Wesam S. Qayed、Mostafa A. Hassan、Wael M. El-Sayed、José Rogério A. Silva、Tarek Aboul-Fadl

  DOI：10.1016/j.bioorg.2022.105884

  日期：2022.9

  Molecular hybrid of 2-indolinone-thiazolidinone is a well known scaffold for variable biological activities including anticancer activity. Accordingly, in the current work aided with structure-based molecular modeling studies, a library of novel twenty-six hybrids, 4(a-z), was designed and synthesized. Docking studies in the active site of CDK2, one of the key checkpoints enzymes, revealed that the

  2-吲哚啉酮-噻唑烷酮的分子杂化物是一种众所周知的支架，具有多种生物活性，包括抗癌活性。因此，在基于结构的分子建模研究的当前工作中，设计和合成了一个新的 26 个杂化物库4(az) 。CDK2（关键检查点酶之一）活性位点的对接研究表明，设计分子的结合分数与参考酶的抑制剂舒尼替尼、尼达尼布和塞马卡尼相当。考虑到阿霉素，这些分子对人肝脏 (HepG2)、乳腺 (MCF7) 和结肠 (HCT-29) 细胞系显示出不同的抗增殖活性作为参考药。与对正常成纤维细胞 (WI-38) 的细胞毒活性相比，测试分子对癌细胞具有更好的选择性，以它们的选择性指数 (SI) 表示，比多柔巴星和化合物 4i是最安全的化合物。化合物4f、4g、4h和4w的 CDK2 抑制结果显示 IC 50分别为 59.43、143.6、27.42 和 61.63 nM，而舒尼替尼为 23.8 nM。为了阐明获得的这些分子的生物活性，