3-hydrazino-4-phenyl-4H-1,2,4-benzothiadiazine 1,1-dioxide | 107089-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 3-hydrazino-4-phenyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 2H-1,2,4-Benzothiadiazin-3(4H)-one, 4-phenyl-, hydrazone, 1,1-dioxide；(1,1-dioxo-4-phenyl-1λ6,2,4-benzothiadiazin-3-yl)hydrazine
• CAS: 107089-81-6
• 化学式: C₁₃H₁₂N₄O₂S
• 分子量: 288.33
• InChiKey: SEYMLDDMBGJEKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-甲基-3戊烯-2-酮 、 3-hydrazino-4-phenyl-4H-1,2,4-benzothiadiazine 1,1-dioxide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以58%的产率得到
  参考文献：
  名称：

  Reddy, A. V. N.; Kamal, Ahmed; Sattur, P. B., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1985, vol. 24, p. 1295 - 1297

  摘要：

  DOI：
• 作为产物：
  描述：

  二苯胺 在 三氯化铝 、 五氯化磷 、 一水合肼 作用下， 以 硝基甲烷 、 氯仿 为溶剂， 反应 1.5h， 生成 3-hydrazino-4-phenyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Anti-tubercular agents. Part 3. Benzothiadiazine as a novel scaffold for anti-Mycobacterium activity

  摘要：

  In an effort to develop new and more effective therapies to treat tuberculosis, a series of benzothiadiazine 1,1-dioxide derivatives were synthesized and their in vitro activity against Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare was evaluated. One of the compounds, 8c, exhibited potent anti-tubercular activity, particularly for the resistant strains and thus prompted us to investigate its in vivo profile. However, the in vivo testing in a mouse model of tuberculosis infection did not show significant anti-tubercular activity, probably because of its poor bioavailability. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.063

文献信息

• Synthesis, DNA-binding ability and evaluation of antitumour activity of triazolo[1,2,4]benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates
  作者：Ahmed Kamal、M. Naseer A. Khan、Y.V.V. Srikanth、K. Srinivasa Reddy、Aarti Juvekar、Subrata Sen、Nisha Kurian、Surekha Zingde

  DOI：10.1016/j.bmc.2008.06.056

  日期：2008.8

  A series of triazolobenzothiadiazine-pyrrolobenzodiazepine conjugates linked through different alkane spacers have been prepared. These compounds have exhibited significant cytotoxicity against most of the cell lines examined. Compound 5a displays GI(50) values from 1.83 to 2.38 microM against seven human tumour cell lines, and is identified as a promising lead compound from this series. Their DNA

  已经制备了通过不同烷烃间隔基连接的一系列三唑并苯并噻二嗪-吡咯并苯并二氮杂pine共轭物。这些化合物对大多数检查的细胞系均表现出明显的细胞毒性。化合物5a对7种人类肿瘤细胞系的GI（50）值从1.83至2.38 microM，被确定为该系列中有希望的先导化合物。他们的DNA热变性研究也已经进行，在孵育36小时后，化合物5c之一将CT-DNA的DNA螺旋熔化温度提高了2.6摄氏度。
• Synthesis, structure analysis, and antibacterial activity of some novel 10-substituted 2-(4-piperidyl/phenyl)-5,5-dioxo[1,2,4]triazolo[1,5-b][1,2,4]benzothiadiazine derivatives
  作者：Ahmed Kamal、M. Naseer A. Khan、K. Srinivasa Reddy、K. Rohini、G. Narahari Sastry、B. Sateesh、B. Sridhar

  DOI：10.1016/j.bmcl.2007.07.043

  日期：2007.10

  10-dihydro[1,2,4]triazolo[1,5-b]-[1,2,4]benzothiadiazine arylsulfonamide derivatives (10a-j and 13a-f) was synthesized. The structures of these compounds were confirmed on the basis of spectral data, elemental analysis, X-ray analysis, and quantum chemical calculations. These compounds were evaluated for their efficacy as antibacterial agents against various Gram-positive and Gram-negative strains of bacteria

  新的10-取代的5,5-二氧-5,10-二氢[1,2,4]三唑[1,5-b]-[1,2,4]苯并噻二嗪芳基磺酰胺衍生物系列（10a-j和13a -f）被合成。这些化合物的结构在光谱数据，元素分析，X射线分析和量子化学计算的基础上得到确认。评价了这些化合物作为针对各种革兰氏阳性和革兰氏阴性细菌的抗菌剂的功效。在这些化合物10f和10i中，对大肠杆菌的活性最高，对大肠杆菌和枯草芽孢杆菌的活性最高的化合物13e。此外，与标准药物相比，其他化合物也显示出有效的抑制活性。
• Anti-tubercular agents. Part IV: Synthesis and antimycobacterial evaluation of nitroheterocyclic-based 1,2,4-benzothiadiazines
  作者：Ahmed Kamal、S. Kaleem Ahmed、K. Srinivasa Reddy、M. Naseer A. Khan、Rajesh V.C.R.N.C. Shetty、B. Siddhardha、U.S.N. Murthy、Inshad Ali Khan、Manoj Kumar、Sandeep Sharma、Anshu Beulah Ram

  DOI：10.1016/j.bmcl.2007.07.027

  日期：2007.10

  In continuation of our earlier work on benzothiadiazines, we have prepared a series of nitrofuran, nitrothiophene and arylfuran coupled benzothiadiazines and evaluated them for antimycobacterial and antibacterial activities. One of the compounds 2f has shown good in vitro antimycobacterial activity. All the synthesized compounds have shown moderate to good antibacterial activity.

  在继续我们对苯并噻二嗪的早期研究工作的过程中，我们制备了一系列硝基呋喃，硝基噻吩和芳基呋喃偶联的苯并噻二嗪，并对它们的抗分枝杆菌和抗菌活性进行了评估。化合物2f之一显示出良好的体外抗分枝杆菌活性。所有合成的化合物均显示出中等至良好的抗菌活性。
• Synthesis and Anticancer Activities of New Benzothiadiazinyl Hydrazinecarboxamides and Anilino[1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-diones
  作者：Ahmed Kamal、Y. V.V. Srikanth、Md. Ashraf、M. Naseer A. Khan、Thokhir Basha Shaik、Shasi V. Kalivendi、Nitasha Suri、A. K. Saxena

  DOI：10.2174/157340611795564259

  日期：2011.5.1

  Two series of compounds (5-14 and 15-23) based on the scaffolds of 2-(1,1-dioxido-4-phenyl-4Hbenzo [e][1,2,4]thiadiazin-3-yl)-N-(4-methoxyphenyl)hydrazinecarboxamide (5) and 2-((4-methoxyphenyl)amino)-10- phenyl-10H-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-dioxide (15) respectively, were designed and synthesized. These compounds were tested for anticancer activity against various cancer cell lines including lung, ovary, prostate, breast and colon cancers. They exhibited moderate to good inhibitory activity against the above cell lines and compound 9 was found to be the most active one from these two series. Further studies showed that cancer cell growth inhibition by compounds 22 and 23 could be in part due to the inhibition of tubulin polymerization, with the IC50 values of 4.70 and 5.25 μM, respectively.

  分别基于2-(1,1-dioxido-4-phenyl-4Hbenzo [e][1,2,4]thiadiazin-3-yl)-N-(4-methoxyphenyl)hydrazinecarboxamide (5)和2-((4-methoxyphenyl)amino)-10- phenyl-10H-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-dioxide (15)骨架的两组化合物（5-14和15-23）被设计并合成。这些化合物被测试对包括肺癌、卵巢癌、前列腺癌、乳腺癌和结肠癌在内的各种癌细胞系的抗癌活性。它们对上述细胞系表现出中等至良好的抑制活性，并且化合物9被发现在这两个系列中是最活跃的。进一步的研究表明，化合物22和23对癌细胞生长的抑制可能部分是由于对微管蛋白聚合的抑制，IC50值分别为4.70和5.25μM。
• 2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers
  作者：Ahmed Kamal、Y.V.V. Srikanth、M. Naseer Ahmed Khan、Md. Ashraf、M. Kashi Reddy、Farheen Sultana、Tandeep Kaur、Gousia Chashoo、Nitasha Suri、Irum Sehar、Zahoor A. Wani、Arpita Saxena、Parduman R. Sharma、Shashi Bhushan、Dilip M. Mondhe、Ajit K. Saxena

  DOI：10.1016/j.bmc.2011.09.060

  日期：2011.12

  A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and 5e) have exhibited potent cytotoxicity specifically against human leukemia HL-60 cell lines with IC50 values in the range of 0.08-0.70 mu M. All these compounds were tested for their effects on the cell cycle perturbations and induction of apoptosis. Morphological evidences of apoptosis, including fragmentation of nuclei and inter nucleosomal DNA laddering formation were clearly observed after 24 h exposure to compound 4i. Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. These compounds trigger the mitochondrial apoptotic pathway that results in the loss of mitochondrial membrane potential through activation of multiple caspases followed by activation of caspase-3, and finally cleavage of PARP. Further the mechanism of cell death was analysed by fluorescent microscopic analysis and also by scanning electron microscopy. The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds. (C) 2011 Elsevier Ltd. All rights reserved.