5-nitro-1H-indole-2,3-dione-3-(4-(4-methylphenyl)thiosemicarbazone) | 518299-08-6

• 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-nitro-1H-indole-2,3-dione-3-(4-(4-methylphenyl)thiosemicarbazone)
• 英文别名: N-(4-methylphenyl)-2-(5-nitro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-1-hydrazinecarbothioamide；2-(5-nitro-2-oxoindolin-3-ylidene)-N-(p-tolyl)hydrazine-1-carbothioamide；1-(4-methylphenyl)-3-[(5-nitro-2-oxoindol-3-yl)amino]thiourea
• CAS: 518299-08-6
• 化学式: C₁₆H₁₃N₅O₃S
• 分子量: 355.377
• InChiKey: GXMRGBYLRDNPLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  25.0
• 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：
  108.66
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-溴丙酸乙酯 、 5-nitro-1H-indole-2,3-dione-3-(4-(4-methylphenyl)thiosemicarbazone) 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 (2E)-5-methyl-2-[(Z)-(5-nitro-2-oxo-indolin-3-ylidene)hydrazono]-3-(p-tolyl)thiazolidin-4-one
  参考文献：
  名称：

  Synthesis and structure–antituberculosis activity relationship of 1H-indole-2,3-dione derivatives

  摘要：

  New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-l-morpholino/piperidinomethyl-1Hindole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-IH-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3dione-3-thiosemicarbazones 4a-1, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.063
• 作为产物：
  描述：

  对甲苯异硫氰酸酯 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 5-nitro-1H-indole-2,3-dione-3-(4-(4-methylphenyl)thiosemicarbazone)
  参考文献：
  名称：

  基于靛红的氨基硫脲衍生物作为 α-葡萄糖苷酶的潜在抑制剂、合成及其分子对接研究

  摘要：

  摘要 合成了一系列新的基于靛红的氨基硫脲衍生物 1-15，并通过 1H NMR、13C NMR 和 HR-EIMS 进行了表征。对合成衍生物的 α-葡萄糖苷酶抑制潜力进行了评估。与 IC50 值为 38.60 ± 0.20 µM 的标准阿卡波糖相比，所有化合物均显示出优异的 α-葡萄糖苷酶抑制潜力，其 IC50 值范围为 1.20 ± 0.10 至 35.60 ± 0.80 µM。IC50 值分别为 2.20 ± 0.10、3.5 ± 0.10、1.20 ± 0.10、5.20 ± 0.20、3.60 ± 0.10、4.60 ± 0.0 和 .0 ± 0 M 的化合物 3、4、5、9、10、12 和 15 分别为 .2 和 0 . 2 。比 IC50 值 38.60 ± 0.20 µM 的标准阿卡波糖好很多倍。所有新合成的化合物也建立了构效关系，主要基于苯环上的取代模式。

  DOI：

  10.1016/j.molstruc.2020.128922

文献信息

• Synthesis and primary cytotoxicity evaluation of new 5-nitroindole-2,3-dione derivatives
  作者：Nilgün Karalı

  DOI：10.1016/s0223-5234(02)01416-2

  日期：2002.11

  A new series of 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (3a-k) obtained by condensation of 5-nitro-1H-indole-2,3dione (1) with N-substituted-thiosemicarbazides (2a-k) were treated with morpholine or piperidine and formaldehyde to yield 1-morpholino/piperidinomethyl-5-nitroindole-2 3-dione-3-thiosemicarbazones (4a-m). The structures of all the compounds were determined by analytical and spectral (IR, H-1-NMR, EIMS) methods. Compounds 3b, 3c, 3f, 3k, 4a, 4c, 4f and 4l chosen as prototypes were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. All the compounds that passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Sulphorhodamine B (SRB) protein assay was used to estimate cell stability or growth. The most active compound was found to be 1-morpholinomethyl-5-nitroindole-2,3-dione-3-N(chlorophenyl)thiosemicarbazone (4l). This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumour cell line in vitro screen on a non-small cell lung cancer cell line (HOP-62, logo GI(50) value < -8.00) and on leukaemia cell lines (HL-60(TB), log(10) GI(50) value -6.30; MOLT-4, log(10) GI(50) value -6.18). (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.
• 5-Nitroisatin-derived thiosemicarbazones: potential antileishmanial agents
  作者：Humayun Pervez、Nazia Manzoor、Muhammad Yaqub、Khalid Mohammed Khan

  DOI：10.3109/14756366.2013.836641

  日期：2014.10.1

  A series of 29 previously reported N(4)-substituted 5-nitroisatin-3-thiosemicarbazones 2-30 has been screened for leishmanicidal potential. Compounds 2-4, 7, 8, 10-13, 15-19, 21, 23, 24, 26, 28 and 30 exhibited good to excellent antileishmanial activities with IC50 values ranging from 0.44 ± 0.02 to 32.38 ± 0.66 µg/mL. Of these, 5, 7, 19 and 28 proved to be the most active antileishmanial agents, displaying activities with IC50 values 1.78 ± 0.35, 0.44 ± 0.02, 1.91 ± 0.04 and 4.28 ± 0.75 µg/mL, respectively, which were even better than the standard drug, pentamidine (IC50 = 5.09 ± 0.04 µg/mL). This study presents the first example of exhibition of leishmanicidal potential by isatin-thiosemicarbazones and as such furnishes a solid basis for further research on these compounds to develop more potent antileishmanial agents.
• Synthesis and biological evaluation of some N4-substituted 5-nitroisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Nazia Manzoor、Muhammad Yaqub、Faiz-ul-Hassan Nasim、Khalid M. Khan

  DOI：10.1007/s00044-011-9745-7

  日期：2012.9

  A series of 5-nitroisatin-3-thiosemicarbazones 2a-2l was synthesised and evaluated for selected biological activities. The brine shrimp lethality bioassay was carried out to study their in vitro cytotoxicity potential and besides, their antifungal, phytotoxic and urease inhibitory effects were also investigated. Only compound 2j proved to be active in the brine shrimp assay exhibiting LD50 value 1.16 x 10(-3) M. Compounds 2a and 2d displayed moderate antifungal activity (50 and 40%, respectively) against M. canis. Similarly, compound 2l exhibited moderate activity (40%) against the fungal strain, A. flavus. In phytotoxicity assay, all the synthesised compounds including the reference point 2m showed weak to moderate (20-60%) activity at the highest tested concentrations (1,000 mu g and 500 mu g/ml, respectively). In urease inhibition assay, compounds 2a, 2i and 2k proved to be potent inhibitors demonstrating pronounced inhibition with IC50 values 0.440, 0.901 and 27.880 mu M, respectively. These compounds may act as leads for further studies.
• Synthesis and structure–antituberculosis activity relationship of 1H-indole-2,3-dione derivatives
  作者：Nilgün Karalı、Aysel Gürsoy、Fatma Kandemirli、Nathaly Shvets、F. Betül Kaynak、Süheyla Özbey、Vasyl Kovalishyn、Anatholy Dimoglo

  DOI：10.1016/j.bmc.2007.05.063

  日期：2007.9.1

  New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-l-morpholino/piperidinomethyl-1Hindole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-IH-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3dione-3-thiosemicarbazones 4a-1, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71. (c) 2007 Elsevier Ltd. All rights reserved.
• Isatin based thiosemicarbazide derivatives as potential inhibitor of α-glucosidase, synthesis and their molecular docking study
  作者：Fazal Rahim、Muhammad Taha、Naveed Iqbal、Shawkat Hayat、Faiza Qureshi、Imad Uddin、Khalid Zaman、Abdur Rab、Abdul Wadood、Nizam Uddin、Muhammad Nawaz、Syed Adnan Ali Shah、Khalid Mohammed Khan

  DOI：10.1016/j.molstruc.2020.128922

  日期：2020.12

  Abstract A new series of isatin based thiosemicarbazide derivatives 1–15 were synthesized and characterized by 1H NMR, 13C NMR and HR-EIMS. The synthetic derivatives were evaluated for α-glucosidase inhibitory potential. All compounds showed excellent α-glucosidase inhibitory potential having IC50 values ranging between 1.20 ± 0.10 to 35.60 ± 0.80 µM when compared with the standard acarbose having

  摘要 合成了一系列新的基于靛红的氨基硫脲衍生物 1-15，并通过 1H NMR、13C NMR 和 HR-EIMS 进行了表征。对合成衍生物的 α-葡萄糖苷酶抑制潜力进行了评估。与 IC50 值为 38.60 ± 0.20 µM 的标准阿卡波糖相比，所有化合物均显示出优异的 α-葡萄糖苷酶抑制潜力，其 IC50 值范围为 1.20 ± 0.10 至 35.60 ± 0.80 µM。IC50 值分别为 2.20 ± 0.10、3.5 ± 0.10、1.20 ± 0.10、5.20 ± 0.20、3.60 ± 0.10、4.60 ± 0.0 和 .0 ± 0 M 的化合物 3、4、5、9、10、12 和 15 分别为 .2 和 0 . 2 。比 IC50 值 38.60 ± 0.20 µM 的标准阿卡波糖好很多倍。所有新合成的化合物也建立了构效关系，主要基于苯环上的取代模式。