5-trifluoromethoxy-1H-indole-2,3-dione 3-[N-(4-fluorophenyl)thiosemicarbazone] | 1084893-03-7

• 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-(4-fluorophenyl)thiosemicarbazone]
• 英文别名: N-(4-fluorophenyl)-2-[2-oxo-5-(trifluoromethoxy)-1,2-dihydro-3H-indol-3-ylidene]-1-hydrazinecarbothioamide；1-(4-fluorophenyl)-3-[[2-oxo-5-(trifluoromethoxy)indol-3-yl]amino]thiourea
• CAS: 1084893-03-7
• 化学式: C₁₆H₁₀F₄N₄O₂S
• 分子量: 398.341
• InChiKey: WMHGCFFXAIDTCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.37
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  吗啉 、 聚合甲醛 、 5-trifluoromethoxy-1H-indole-2,3-dione 3-[N-(4-fluorophenyl)thiosemicarbazone] 以 乙醇 为溶剂， 反应 10.0h， 以76%的产率得到5-trifluoromethoxy-1-(morpholin-4-ylmethyl)-1H-indole-2,3-dione 3-[N-(4-fluorophenyl)thiosemicarbazone]
  参考文献：
  名称：

  Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.08.050
• 作为产物：
  描述：

  4-(4-氟苯)-3-氨基硫脲 、 5-三氟甲氧基吲哚-2,3-二酮 在 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以76%的产率得到5-trifluoromethoxy-1H-indole-2,3-dione 3-[N-(4-fluorophenyl)thiosemicarbazone]
  参考文献：
  名称：

  Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones

  摘要：

  通过三氟甲氧基异吲哚1与不同芳基缩氨基脲2在含有几滴醋酸的50%乙醇水溶液中的反应，合成了一系列21种N4-芳基取代的5-三氟甲氧基异吲哚-3-缩氨基脲3a-3u。它们的结构是基于分析（CHN）和光谱（IR，1H-NMR，EIMS）数据确定的。所有合成的化合物都通过卤虫致死生物测定法评估了它们的毒性潜力。其中10种化合物，即3a，3e，3i-3l和3n-3q在此测定中表现活跃，显示出有前景的毒性（LD50 = 1.11 × 10−5 M − 1.80 × 10−4 M）。在这些化合物中，3k，3n和3o被发现是最活跃的（LD50 = 1.11 × 10−5 M − 1.43 × 10−5 M）。化合物3k显示出最高的活性，其LD50值为1.11 × 10−5 M，因此可以作为进一步研究的先导化合物。构效关系（SAR）研究表明，在异吲哚部分的5位上存在强诱导电子吸引的三氟甲氧基取代基，在诱导或增强某些合成化合物的毒性潜力方面发挥了重要作用。

  DOI：

  10.3390/molecules16086408

文献信息

• Synthesis, biological evaluation and docking studies of some novel isatin-3-hydrazonothiazolines
  作者：Maqbool Ahmad、Humayun Pervez、Sumera Zaib、Muhammad Yaqub、Muhammad Moazzam Naseer、Shafi Ullah Khan、Jamshed Iqbal

  DOI：10.1039/c6ra10043k

  日期：——

  The putative binding mode of compound 6i in the active site of Jack bean urease.

  豆腐脲酶活性部位中化合物6i的推定结合方式。
• 5‐Fluoro/(trifluoromethoxy)‐2‐indolinone derivatives with anti‐interleukin‐1 activity
  作者：Özge Soylu‐Eter、Zekiye Şeyma Sevinçli、Betül Ersoy、Bahar Hasanusta、Uğur Gatfar、Nathan A. Lack、Burak Erman、Ahmet Gül、Hakan S. Orer、Nilgün Karalı

  DOI：10.1002/ardp.202300217

  日期：2023.12

  2-indolinone derivatives in preliminary studies to develop agents with anti-IL-1 activity. First, the putative efficacies and binding interactions of 2-indolinones were evaluated by docking studies. Second, previously synthesized 5-fluoro/(trifluoromethoxy)−1H-indole-2,3-dione 3-(4-phenylthiosemicarbazones) (compounds 47–69) which had the highest inhibitory effect in the screening were evaluated for inhibitory

  促炎细胞因子白介素-1 (IL-1) 驱动多种炎症性疾病的发病机制。最近的研究表明，2-吲哚酮可以调节细胞因子反应。因此，我们在初步研究中筛选了几种2-二氢吲哚酮衍生物，以开发具有抗IL-1活性的药物。首先，通过对接研究评估了 2-吲哚酮的假定功效和结合相互作用。其次，评估了先前合成的在筛选中具有最高抑制效果的5-氟/(三氟甲氧基)−1 H-吲哚-2,3-二酮3-(4-苯硫代缩氨基脲)（化合物47-69 ）的抑制效果。 IL-1 受体 (IL-1R)。选择化合物52 (IC 50 = 0.09 µM) 和65 (IC 50 = 0.07 µM) 作为先导化合物，用于随后合成新衍生物。设计、合成了新型5-氟/(三氟甲氧基)−1 H-吲哚-2,3-二酮3-(4-苯硫代缩氨基脲)（化合物70-116 ），并完成了体外研究。测试的化合物76 、 78 、 81 、 91 、 100 、 105和107在
• 10.1016/j.bioorg.2024.107481
  作者：Ahn, Seunghyun、Yeo, Hyunjin、Jung, Euitaek、Lee, Youngshim、Koh, Dongsoo、Lee, Hyeonhwa、Han Lee, Young、Lim, Yoongho、Young Shin, Soon

  DOI：10.1016/j.bioorg.2024.107481

  日期：——
• 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.
• Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Naveeda Saira、Mohammad Saeed Iqbal、Muhammad Yaqub、Khalid Mohammed Khan

  DOI：10.3390/molecules16086408

  日期：——

  A series of twenty one N4-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%), containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN) and spectral (IR, 1H-NMR, EIMS) data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD50 = 1.11 × 10−5 M − 1.80 × 10−4 M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD50 = 1.11 × 10−5 M − 1.43 × 10−5 M). Compound 3k showed the highest activity with a LD50 value of 1.11 × 10−5 M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR) studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds.

  通过三氟甲氧基异吲哚1与不同芳基缩氨基脲2在含有几滴醋酸的50%乙醇水溶液中的反应，合成了一系列21种N4-芳基取代的5-三氟甲氧基异吲哚-3-缩氨基脲3a-3u。它们的结构是基于分析（CHN）和光谱（IR，1H-NMR，EIMS）数据确定的。所有合成的化合物都通过卤虫致死生物测定法评估了它们的毒性潜力。其中10种化合物，即3a，3e，3i-3l和3n-3q在此测定中表现活跃，显示出有前景的毒性（LD50 = 1.11 × 10−5 M − 1.80 × 10−4 M）。在这些化合物中，3k，3n和3o被发现是最活跃的（LD50 = 1.11 × 10−5 M − 1.43 × 10−5 M）。化合物3k显示出最高的活性，其LD50值为1.11 × 10−5 M，因此可以作为进一步研究的先导化合物。构效关系（SAR）研究表明，在异吲哚部分的5位上存在强诱导电子吸引的三氟甲氧基取代基，在诱导或增强某些合成化合物的毒性潜力方面发挥了重要作用。