(Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-(4-fluorophenyl)hydrazinecarbothio amide | 948998-10-5

• 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: (Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-(4-fluorophenyl)hydrazinecarbothio amide
• 英文别名: 1-[(5-fluoro-2-oxoindol-3-yl)amino]-3-(4-fluorophenyl)thiourea
• CAS: 948998-10-5
• 化学式: C₁₅H₁₀F₂N₄OS
• 分子量: 332.333
• InChiKey: GSMVVGKPNQDCDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.61
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.52
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-(4-fluorophenyl)hydrazinecarbothio amide 、 2'-溴-4-氯苯乙酮 以88%的产率得到(3Z)-5-fluoro-1H-indole-2,3-dione 3-{[(2Z)-4-(4-chlorophenyl)-3-(4-fluorophenyl)-1,3-thiazol-2(3H)-ylidene]hydrazone}
  参考文献：
  名称：

  某些新型isatin-3-hydrazonothiazolines的合成，生物学评估和对接研究

  摘要：

  豆腐脲酶活性部位中化合物6i的推定结合方式。

  DOI：

  10.1039/c6ra10043k
• 作为产物：
  描述：

  4-氟苯基异硫氰酸酯 在 硫酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 生成 (Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-(4-fluorophenyl)hydrazinecarbothio amide
  参考文献：
  名称：

  具有抗 IL-1 活性的 5-氟/(三氟甲氧基)-2-二氢吲哚酮衍生物

  摘要：

  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

  DOI：

  10.1002/ardp.202300217

文献信息

• 一种PTP1B抑制剂及其合成方法和用途
  申请人：复旦大学

  公开号：CN114634500A

  公开（公告）日：2022-06-17

  本发明属于医药技术领域，具体为一种含5‑取代‑3‑(3‑芳基取代噻唑烷‑4‑酮‑2‑叉基亚肼基)吲哚‑2‑酮类衍生物及其合成方法和应用。本发明利用拼合原理、药效团模型以及PTP1B抑制剂的结构特征，结合PTP1B酶活性位点的特性，设计合成具有生物碱吲哚‑3‑取代1,3‑噻唑烷‑4‑酮基本结构的化合物。体外对PTP1B酶抑制活性测试表明：本发明化合物在浓度为5μg/mL下都显示出了良好的PTP1B抑制活性，抑制率为50％以上，其半数抑制浓度(IC50值)在0.45～14.53μM之间；抑制率最高达92.70％，活性最好的IC50值达0.45μM，可成为PTP1B抑制剂的先导化合物。对接结果表明所设计的化合物与酶的多个作用位点都有很好的相互作用，包括氢键，疏水相互作用，范德华力等。
• 含吲哚生物碱杂环取代-1,3-噻唑烷酮类衍生物及其制备方法和用途
  申请人：复旦大学

  公开号：CN114634503A

  公开（公告）日：2022-06-17

  本发明属于医药技术领域，具体为一种含生物碱1H‑吲哚‑3‑取代‑1,3‑噻唑烷‑4‑酮类衍生物及其合成方法和应用。本发明利用拼合原理、药效团模型以及PTP1B抑制剂的结构特征，结合PTP1B酶活性位点的特点，设计合成具有生物碱1H‑吲哚‑3‑取代‑1,3‑噻唑烷‑4‑酮基本结构的化合物；本发明还包含其药用盐，水合物及溶剂化物，其多晶或共晶，其同样生物功能的前体和衍生物。测试表明：该化合物体外对PTP1B酶具有良好的抑制活性；实施例合成的14个化合物在浓度为5μg/mL下都显示出优秀的PTP1B抑制活性，其半数抑制浓度(IC50值)在4.56～14.53μM之间，抑制率最高达80.61％，活性最好的IC50值为4.56μM，可成为PTP1B抑制剂的潜在先导化合物。
• 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
• Synthesis and biological evaluation of some N 4-aryl-substituted 5-fluoroisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Naveeda Saira、Mohammad Saeed Iqbal、Muhammad Yaqub、Khalid Mohammed Khan

  DOI：10.1007/s00044-013-0575-7

  日期：2013.12

  A series of N (4)-aryl-substituted 5-fluoroisatin-3-thiosemicarbazones 3a-3l was synthesized 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. Seven compounds i.e. 3a, 3d, 3f, 3g, 3h, 3j and 3k proved to be active in the brine shrimp assay, displaying promising cytotoxicity (LD50 = 6.89 x 10(-5)-2.79 x 10(-4) M). Amongst these, 3a and 3h were found to be the most active ones (LD50 = 6.89 x 10(-5) and 9.79 x 10(-5) M, respectively). Compounds 3i, 3j and 3 k displayed moderate (40 %) antifungal activity against one or two fungal strains i.e. A. flavus and/or M. canis. In phytotoxicity assay, all the synthesized compounds, including the reference point 2m showed weak-to-moderate (15-70 %) activity at the highest tested concentration (500 mu g/mL). In urease inhibition assay, compounds 3f, 3g and 3j proved to be the most potent inhibitors, demonstrating relatively a higher degree of enzymatic inhibition with IC50 values ranging from 37.7 to 47.3 mu M.
• 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.