6-chloro-7-methyl-3-methylthio-1,4,2-benzodithiazin 1,1-dioxide

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-chloro-7-methyl-3-methylthio-1,4,2-benzodithiazin 1,1-dioxide
• 英文别名: 6-chloro-7-methyl-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide；6-chloro-1,1-dioxo-7-methyl-3-methylthio-1,4,2-benzodithiazine；6-chloro-7-methyl-3-methylsulfanyl-1λ6,4,2-benzodithiazine 1,1-dioxide
• 化学式: C₉H₈ClNO₂S₃
• 分子量: 293.819
• InChiKey: KLIVHFZFNPOWMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-7-methyl-3-methylthio-1,4,2-benzodithiazin 1,1-dioxide 在 sodium hydroxide 作用下， 以 丙酮 、 xylene 为溶剂， 反应 13.0h， 生成 6-chloro-3-hydroxy-7-methyl-1,4,2-benzo-dithiazine 1,1-dioxide
  参考文献：
  名称：

  Brzozowski, Zdzislaw, Acta Poloniae Pharmaceutica, 1994, vol. 51, # 1, p. 69 - 76

  摘要：

  DOI：
• 作为产物：
  描述：

  2,4-二氯甲苯 在 盐酸 、 氯磺酸 、 ammonium hydroxide 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 65.25h， 生成 6-chloro-7-methyl-3-methylthio-1,4,2-benzodithiazin 1,1-dioxide
  参考文献：
  名称：

  Molecular editing of NSC-666719 enabling discovery of benzodithiazinedioxide-guanidines as anticancer agents

  摘要：

  In this study, a unique strategy of scaffold-hopping-based molecular editing of a bioactive agent NSC-666719 was investigated, which led to the development of new benzodithiazinedioxide-guanidine based anticancer agents with Polβ inhibition.

  DOI：

  10.1039/d3md00648d

文献信息

• Synthesis of a new series of biologically interesting 6′-chloro-1′,1′-dioxospiro[4H-benzo[d][1,3,7]oxadiazocine-4,3′(2′H)-[1,4,2]benzodithiazine]-2,6(1H,5H)dione derivatives
  作者：Zdzisław Brzozowski、Beata Żołnowska、Jarosław Sławiński

  DOI：10.1007/s00706-013-1010-y

  日期：2013.9

  AbstractA series of 6′-chloro-1′,1′-dioxospiro[4H-benzo[d][1,3,7]oxadiazocine-4,3′(2′H)-[1,4,2]benzodithiazine]-2,6(1H,5H)dione derivatives have been synthesized from isatoic anhydride and 3-(R2-amino)-1,4,2-benzodithiazine 1,1-dioxides. Some synthetic limitations are discussed on the basis of quantum chemical calculations performed by use of the Hartree–Fock method. Graphical Abstract

  摘要一系列6'-氯-1'，1'-二氧代-螺〔4 ħ -苯并[ d ] [1,3,7] oxadiazocine-4,3'（2' ħ） - [1,4,2] benzodithiazine由等角酸酐和3-（R 2-氨基）-1,4,2-苯并噻二嗪1,1-二氧化物合成了] -2,6（1 H，5 H）二酮衍生物。在使用Hartree-Fock方法进行量子化学计算的基础上，讨论了一些合成限制。 图形概要
• Synthesis and QSAR Study of Novel 6-Chloro-3-(2-Arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-Dioxide Derivatives with Anticancer Activity
  作者：Jarosław Sławiński、Beata Żołnowska、Zdzisław Brzozowski、Anna Kawiak、Mariusz Belka、Tomasz Bączek

  DOI：10.3390/molecules20045754

  日期：——

  A series of new 6-chloro-3-(2-arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives were effectively synthesized from N-methyl-N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazines. The intermediate compounds as well as the products, were evaluated for their cytotoxic effects toward three human cancer cell lines. All compounds shown moderate or weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compound 16 exhibited the most potent cytotoxic activity against the HeLa cell line, with an IC50 value of 10 µM, while 14 was the most active against the MCF-7 and HCT-116 cell lines, affording IC50 values of 15 µM and 16 µM, respectively. The structure-activity relationship was evaluated based on QSAR methodology. The QSAR MCF-7 model indicated that natural charge on carbon atom C13 and energy of highest occupied molecular orbital (HOMO) are highly involved in cytotoxic activity against MCF-7 cell line. The cytotoxic activity of compounds against HCT-116 cell line is dependent on natural charge on carbon atom C13 and electrostatic charge on nitrogen atom N10. The obtained QSAR models could provide guidelines for further development of novel anticancer agents.

  一系列新的6-氯-3-(2-芳基亚甲基-1-甲基肼)-1,4,2-苯并二噁嗪1,1-二氧化物衍生物有效地合成于N-甲基-N-(6-氯-1,1-二氧代-1,4,2-苯并二噁嗪-3-基)肼。中间化合物及最终产品被评估对三种人类癌细胞系的细胞毒性效果。所有化合物对所测试的癌细胞系表现出中等或弱的细胞毒性效果，但观察到选择性的细胞毒性效果。化合物16对HeLa细胞系表现出最强的细胞毒活性，其IC50值为10 µM，而化合物14在对MCF-7和HCT-116细胞系的活性最强，IC50值分别为15 µM和16 µM。基于QSAR方法评估了结构-活性关系。QSAR MCF-7模型表明，碳原子C13的自然电荷和最高占据分子轨道(HOMO)的能量与对MCF-7细胞系的细胞毒活性高度相关。化合物对HCT-116细胞系的细胞毒活性依赖于碳原子C13的自然电荷和氮原子N10的静电电荷。获得的QSAR模型可为进一步开发新型抗癌药物提供指导。
• Synthesis, anti-HIV-1 integrase, and cytotoxic activities of 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives
  作者：Zdzisław Brzozowski、Jarosław Sławiński、Franciszek Sączewski、Tino Sanchez、Nouri Neamati

  DOI：10.1016/j.ejmech.2007.08.013

  日期：2008.6

  Several 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives 13-28 and 35-44 have been synthesized and tested as potential HIV-1 integrase (IN) inhibitors. Compounds 15-17, 19, 21-28, 36 and 41 inhibited IN with IC(50) values in the range of 3.3-63.0 microM. The compounds 13, 15, 16, 21-24 and 26-28 were further tested at the US National Cancer Institute for their in vitro activity

  几种4-氯-N-（4-氧嘧啶基-2-基）-2-巯基苯磺酰胺衍生物13-28和35-44已被合成并作为潜在的HIV-1整合酶（IN）抑制剂进行了测试。化合物15-17、19、21-28、36和41抑制IN的IC（50）值在3.3-63.0 microM之间。在美国国家癌症研究所进一步测试了化合物13、15、16、21-24和26-28的抗53-57种人类肿瘤细胞系的体外活性。化合物26-28是无活性的，而其他化合物对一种或多种人类肿瘤细胞系表现出高或合理的活性（GI（50）<0.01-20.0 microM）。
• Synthesis and anti-HIV-1 activity of a novel series of 1,4,2-benzodithiazine-dioxides
  作者：Zdzisław Brzozowski、Franciszek Sączewski、Nouri Neamati

  DOI：10.1016/j.bmcl.2006.07.089

  日期：2006.10

  we discovered a series of novel benzodithiazines-dioxides with both antiviral and anticancer activities. In order to design compounds with distinct antiviral properties, we prepared new compounds with modifications on the imidazole and pyrimidine rings. Herein, we present the synthesis and antiviral activity of 8-chloro-2,3-dihydroimidazo[1,2-b][1,4,2]benzodithiazine 5,5-dioxides (22, 23, 30, and 31)

  以前，我们发现了一系列具有抗病毒和抗癌活性的新型二苯并噻嗪类二氧化物。为了设计具有独特抗病毒特性的化合物，我们制备了在咪唑和嘧啶环上经过修饰的新化合物。在这里，我们介绍了8-氯-2,3-二氢咪唑并[1,2-b] [1,4,2]苯并噻二嗪5,5-二氧化物（22、23、30和31）的合成和抗病毒活性，以及9-氯-2,3,4-三氢嘧啶基[1,2-b] [1,4,2]苯并噻二嗪6,6-二氧化物（14、24、25和27）。我们成功地鉴定出具有显着抗HIV-1活性（EC（50）= 0.09microM）的先导化合物。这些化合物显示出最小的细胞毒性，因此适用于抗病毒开发。
• Synthesis and anti-HIV activity of<i>n</i>-(3-amino-3,4-dihydro-4-oxopyrimidin-2-yl)-4-chloro-2-mercapto-5-methylbenzenesulfonamide derivatives
  作者：Zdzislaw Brzozowski、Franciszek Sączewski

  DOI：10.1002/jhet.5570440144

  日期：2007.1

  A series of N-(3-amino-3,4-dihydro-4-oxopyrimidin-2-yl)-4-chloro-2-mercapto-5-methylbenzenesulfonamide derivatives 10-17 have been synthesized as potential anti-HIV agents. The in vitro anti-HIV-1 activity of these compounds has been tested at the national Cancer Institute (Bethesda, MD), and the structure-activity relationships are discussed. The selected N-[3-amino-3,4-dihydro-6-(tert-butyl)-4-oxothieno[2

  已经合成了一系列的N-（3-氨基-3,4-二氢-4-氧嘧啶丁-2-基）-4-氯-2-巯基-5-甲基苯磺酰胺衍生物10-17作为潜在的抗HIV剂。在体外，这些化合物的抗HIV-1活性已经在国家癌症研究所（贝塞斯达，MD）进行了测试，并且该结构-活性关系进行了探讨。选定的N- [3-氨基-3,4-二氢-6-（叔丁基）-4-氧噻吩并[2,3 - e ]嘧啶-2-基] -4-氯-2-巯基-5-甲基苯磺酰胺（14）表现出良好的抗HIV-1活性，其50％有效浓度（EC 50）值为15μM，细胞毒性作用较弱（IC 50 = 106μM）。