(Z)-N’-(5-fluoro-2-oxoindolin-3-ylidene)isonicotinohydrazide | 283584-54-3

• 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)-N’-(5-fluoro-2-oxoindolin-3-ylidene)isonicotinohydrazide
• 英文别名: (Z)-N'-(5-fluoro-2-oxoindolin-3-ylidene)isonicotinohydrazide；N'-(5-fluoro-2-oxoindol-3-yl)pyridine-4-carbohydrazide
• CAS: 283584-54-3
• 化学式: C₁₄H₉FN₄O₂
• mdl: MFCD01248276
• 分子量: 284.249
• InChiKey: QZRVNZGGTGCJEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  21.0
• 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：
  83.45
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 (Z)-N’-(5-fluoro-2-oxoindolin-3-ylidene)isonicotinohydrazide 、 加替沙星 以 乙醇 为溶剂， 以62.1%的产率得到1-cyclopropyl-6-fluoro-7-[4-[[5-fluoro-2-oxo-3-(pyridine-4-carbonylhydrazinylidene)indol-1-yl]methyl]-3-methylpiperazin-1-yl]-8-methoxy-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Gatifloxacin derivatives: Synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis DNA gyrase

  摘要：

  Sixteen 7-substituted gatifloxacin derivatives were synthesized and evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. tuberculosis. Among the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy-7-[[[N-4-[I'-(5-isatinyl-beta-semicarbazo)]methyl]3-methyl]N-1-piperazinyl]-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (3d) was found to be the most active compound in vitro with an MIC of 0.0125 mu g/mL against MTB and MTR-TB. In the in vivo animal model 3d decreased the bacterial load in lung and spleen tissues with 3.62- and 3.76-log 10 protections, respectively. Compound 3d was also found to be equally active as gatifloxacin in the inhibition of the supercoiling activity of wild-type M. tuberculosis DNA gyrase with an IC50 of 3.0 mu g/mL. The results demonstrate the potential and importance of developing new quinolone derivatives against mycobacterial infections. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.02.065
• 作为产物：
  描述：

  异烟肼 、 5-氟靛红 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以86 %的产率得到(Z)-N’-(5-fluoro-2-oxoindolin-3-ylidene)isonicotinohydrazide
  参考文献：
  名称：

  作为潜在抗糖尿病药物的新型靛红-酰肼偶联物的合成及生物学评价

  摘要：

  糖尿病是一种严重的代谢紊乱病症，其患病率非常高，并导致其他健康破坏性并发症。胰腺胰岛素抵抗和β-细胞功能障碍是导致高血糖水平的决定性特征。本研究的目的是找到可能具有阻断 α-葡萄糖苷酶的抗高血糖作用的物质。对于这些研究，合成了几种新型吲哚-酰肼偶联物 ( 3a–3r )，并使用各种光谱方法对其进行了检测。将3a–3r系列的研究化合物与参考药物阿卡波糖 1C 50  = 873.34 ± 1.67  µ M 进行比较，所有化合物均表现出对 α-葡萄糖苷酶的有效抑制作用，IC 50值在 0.51–42.91 µ M范围内。 最高抑制作用见于类似物3p和3o，其 IC 50值 分别为 0.51 ± 0.06 和 1.57 ± 0.08 µM 。构效关系表明，这些化合物的 α-葡萄糖苷酶潜力随新型吲哚-酰肼上的各种取代基模式而变化。动力学和对接检测表明，活性化合物很好地适应了 α-葡萄糖苷酶的活性位点，并表现出混合型抑制作用。

  DOI：

  10.1016/j.molstruc.2023.135783

文献信息

• Schiff Bases of Indoline-2,3-dione: Potential Novel Inhibitors of Mycobacterium Tuberculosis (Mtb) DNA Gyrase
  作者：Tarek Aboul-Fadl、Hatem A. Abdel-Aziz、Mohammed K. Abdel-Hamid、Tilal Elsaman、Jane Thanassi、Michael J. Pucci

  DOI：10.3390/molecules16097864

  日期：——

  In the present study a series of Schiff bases of indoline-2,3-dione were synthesized and investigated for their Mtb gyrase inhibitory activity. Promising inhibitory activity was demonstrated with some of these derivatives, which exhibited IC50 values ranging from 50–157 mM. The orientation and the ligand-receptor interactions of such molecules within the Mtb DNA gyrase A subunit active site were investigated applying a multi-step docking protocol using Molecular Operating Environment (MOE) and Autodock4 docking software. The results revealed the importance of the isatin moiety and the connecting side chain for strong interactions with the enzyme active site. Among the tested compounds the terminal aromatic ring benzofuran showed the best activity. Promising new leads for developing a novel class of Mtb gyrase inhibitors were obtained from Schiff bases of indoline-2,3-dione.

  在本研究中，合成了一系列吲哚啉-2,3-二酮的施夫碱，并研究了它们对结核分枝杆菌（Mtb）拓扑异构酶抑制活性。其中一些衍生物显示出良好的抑制活性，IC50值范围为50–157 mM。通过采用多步骤的对接方案，利用分子操作环境（MOE）和Autodock4对接软件，研究了这些分子在Mtb DNA拓扑异构酶A亚基活性位点内的取向和配体-受体相互作用。结果揭示了异羧酸基团及连接侧链在与酶活性位点强相互作用中的重要性。在测试的化合物中，末端芳香环苯并呋喃表现出最佳活性。从吲哚啉-2,3-二酮的施夫碱中获得了开发新型Mtb拓扑异构酶抑制剂的有希望的新线索。
• Gatifloxacin derivatives: Synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis DNA gyrase
  作者：Dharmarajan Sriram、Alexandra Aubry、Perumal Yogeeswari、L.M. Fisher

  DOI：10.1016/j.bmcl.2006.02.065

  日期：2006.6

  Sixteen 7-substituted gatifloxacin derivatives were synthesized and evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. tuberculosis. Among the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy-7-[[[N-4-[I'-(5-isatinyl-beta-semicarbazo)]methyl]3-methyl]N-1-piperazinyl]-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (3d) was found to be the most active compound in vitro with an MIC of 0.0125 mu g/mL against MTB and MTR-TB. In the in vivo animal model 3d decreased the bacterial load in lung and spleen tissues with 3.62- and 3.76-log 10 protections, respectively. Compound 3d was also found to be equally active as gatifloxacin in the inhibition of the supercoiling activity of wild-type M. tuberculosis DNA gyrase with an IC50 of 3.0 mu g/mL. The results demonstrate the potential and importance of developing new quinolone derivatives against mycobacterial infections. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of novel isatin-hydrazide conjugates as potential antidiabetic agents
  作者：Rima D. Alharthy、Syeda Bakhtawar Zahra、Noor Fatima、Arooma Tabassum、Saeed Ullah、Sobia Ahsan Halim、Ajmal Khan、Javid Hussain、Ahmed Al-Harrasi、Zahid Shafiq

  DOI：10.1016/j.molstruc.2023.135783

  日期：2023.9

  features resulting in high blood glucose level. This study's objective was to locate substances with possible anti-hyperglycemic effect that block α-glucosidase. For these studies several novel indole-hydrazide conjugates (3a–3r) were synthesized and examined using a variety of spectroscopic methods. Comparing the investigated compounds from the 3a–3r series to the reference medication acarbose 1C50 = 873

  糖尿病是一种严重的代谢紊乱病症，其患病率非常高，并导致其他健康破坏性并发症。胰腺胰岛素抵抗和β-细胞功能障碍是导致高血糖水平的决定性特征。本研究的目的是找到可能具有阻断 α-葡萄糖苷酶的抗高血糖作用的物质。对于这些研究，合成了几种新型吲哚-酰肼偶联物 ( 3a–3r )，并使用各种光谱方法对其进行了检测。将3a–3r系列的研究化合物与参考药物阿卡波糖 1C 50  = 873.34 ± 1.67  µ M 进行比较，所有化合物均表现出对 α-葡萄糖苷酶的有效抑制作用，IC 50值在 0.51–42.91 µ M范围内。 最高抑制作用见于类似物3p和3o，其 IC 50值 分别为 0.51 ± 0.06 和 1.57 ± 0.08 µM 。构效关系表明，这些化合物的 α-葡萄糖苷酶潜力随新型吲哚-酰肼上的各种取代基模式而变化。动力学和对接检测表明，活性化合物很好地适应了 α-葡萄糖苷酶的活性位点，并表现出混合型抑制作用。