6-chloro-7-cyano-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide | 198694-41-6

• 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-cyano-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide
• 英文别名: 6-chloro-7-cyano-3-methylthio-1,1-dioxo-1,4,2-benzodithiazine；6-Chloro-3-methylsulfanyl-1,1-dioxo-1lambda6,4,2-benzodithiazine-7-carbonitrile；6-chloro-3-methylsulfanyl-1,1-dioxo-1λ6,4,2-benzodithiazine-7-carbonitrile
• CAS: 198694-41-6
• 化学式: C₉H₅ClN₂O₂S₃
• 分子量: 304.802
• InChiKey: MEWISYWQGMHRLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  17.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  70.29
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6-chloro-7-cyano-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以89%的产率得到S-methyl N-(4-chloro-5-cyano-2-mercaptobenzenesulphonyl)thiocarbamate
  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：

  6-chloro-3-metylotio-1,1-diokso-1,4,2-benzoditiazyno-7-karboksyamid 在 三氯氧磷 作用下， 反应 10.0h， 以82%的产率得到6-chloro-7-cyano-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide
  参考文献：
  名称：

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

  摘要：

  DOI：

文献信息

• 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。
• Carbonic anhydrase inhibitors: Synthesis and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with 4-substituted 3-pyridinesulfonamides
  作者：Zdzisław Brzozowski、Jarosław Sławiński、Franciszek Sączewski、Alessio Innocenti、Claudiu T. Supuran

  DOI：10.1016/j.ejmech.2010.02.020

  日期：2010.6

  A series of novel 4-substituted-3-pyridinesulfonamides (2-27 and 31-33) have been synthesized and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase (CA, EC 42 11), that is, the cytosolic, ubiquitous isozymes CA I and II, and transmembrane isozymes CA IX, XII (cancer-associated) and XIV. Against the human isozymes hCA I, the new compounds showed inhibition constants in the range of 0.078-11.7 mu M, against hCA II in the range of 9.9-140 nM, against hCA IX in the range of 4.6-313 nM, against hCA XII in the range of 3.4-21.6 nM, and against hCA XIV in the range of 50.9-160 nM, respectively. Compounds 4, 6, 7, 9, 11-14, 19, 20, 22-24, 26, 27, 31 and 32 showed excellent hCA IX inhibitory efficacy, with inhibition constants of 4.6-12 0 nM, being much more effective as compared to the clinically used sulfonamides AAZ, MZA, EZA, DCP and IND 4-[N'-(6-Chloro-7-cyano-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazino]-3-pyridinesulfonamide (31) is the prominent of the compounds due to its remarkable inhibitory activity toward hCA I (K(I)s = 0.078 mu M), hCA IX (K(I)s = 7.2 nM) and hCA XII (K(I)s = 3.4 nM).
• Brzozowski, Zdzislaw, Acta poloniae pharmaceutica, 1997, vol. 54, # 4, p. 293 - 298
  作者：Brzozowski, Zdzislaw

  DOI：——

  日期：——
• Brzozowski; Saczewski, Polish Journal of Chemistry, 2005, vol. 79, # 10, p. 1659 - 1666
  作者：Brzozowski、Saczewski

  DOI：——

  日期：——