6-硝基-2-[(6-硝基-1,3-苯并噻唑-2-基)二硫烷基]-1,3-苯并噻唑 | 121579-06-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 6-硝基-2-[(6-硝基-1,3-苯并噻唑-2-基)二硫烷基]-1,3-苯并噻唑
• 英文名称: bis(6-nitrobenzo[d]thiazol-2-yl)disulfide
• 英文别名: Benzothiazole, 2,2'-dithiobis[6-nitro-；6-nitro-2-[(6-nitro-1,3-benzothiazol-2-yl)disulfanyl]-1,3-benzothiazole
• CAS: 121579-06-4
• 化学式: C₁₄H₆N₄O₄S₄
• 分子量: 422.49
• InChiKey: MFCGAIPEIISLHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  225
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-硝基-2-[(6-硝基-1,3-苯并噻唑-2-基)二硫烷基]-1,3-苯并噻唑 在 sodium hydroxide 、 potassium permanganate 、 二乙二醇丁醚 、 溶剂黄146 、 sodium sulfite 作用下， 生成 2-甲基磺酰基-6-硝基苯并噻唑
  参考文献：
  名称：

  “Nitro Captax”—6-Nitro-2-mercaptobenzothiazole—as a Reagent for the Identification of Alkyl Halides¹

  摘要：

  DOI：

  10.1021/ja01196a024
• 作为产物：
  描述：

  二硫化二苯并噻唑 在 硫酸 、 硝酸 作用下， 反应 1.0h， 以71%的产率得到6-硝基-2-[(6-硝基-1,3-苯并噻唑-2-基)二硫烷基]-1,3-苯并噻唑
  参考文献：
  名称：

  Development of the First Generation of Disulfide-Based Subtype-Selective and Potent Covalent Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors

  摘要：

  Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, on the basis of the scaffold of 16, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analogue, 3a, effectively inhibits PDK1 both at the molecular (k(mact)/K-i = 4.17 x 10(3) M-1 s(-1)) and the cellular level (down to 0.1 mu M). In contrast to 16, 3a is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2-4. 3a also significantly alters glucose metabolic pathways in A549 cells by decreasing ECAR and increasing ROS. Moreover, in the xenograft models, 3a shows significant antitumor activity with no negative effect to the mice weight. Collectively, these data demonstrate that 3a may be an excellent lead compound for the treatment of cancer as a first-generation subtype-selective and covalent PDK1 inhibitor.

  DOI：

  10.1021/acs.jmedchem.6b01245
• 作为试剂：
  描述：

  Benzyl 2-[3-phenoxyacetamido-4-(6-nitrobenzothiazol-2-yldithio)-2-azetidinon-1-yl]-3-methyl-3-butenoate 、 6-Nitrobenzothiazol-2-yl benzenethiosulfonate 、 水 、 sodium;benzenesulfinate 在 6-硝基-2-[(6-硝基-1,3-苯并噻唑-2-基)二硫烷基]-1,3-苯并噻唑 作用下， 以 丙酮 为溶剂， 反应 8.0h， 以giving benzyl 2-(3-phenoxyacetamido-4-benzenesulfonylthio-2-azetidinon-1-yl)-3-methyl-3-butenoate in a yield of 79%的产率得到benzyl 2-(3-phenoxyacetamido-4-benzenesulfonylthio-2-azetidinon-1-yl)-3-methyl-3-butenoate
  参考文献：
  名称：

  Process for preparation of 4-sulfonylthio azetidinone derivatives

  摘要：

  一种制备式为##STR1##的氮杂环丙酮衍生物的方法，其中R.sup.1是氢、卤素或低级烷氧基，R.sup.2是氢、卤素、低级烷氧基、氨基或者一个基团##STR2##（其中R.sup.5是取代或未取代的苯基、取代或未取代的苯甲基、取代或未取代的苯氧甲基或取代或未取代的苯甲酰基），或者当R.sup.1和R.sup.2结合在一起时，它们是羰基，R.sup.3是取代或未取代的苯基，R.sup.4是氢、可选取代的碳氢残基或来自无机酸或有机酸的酰基、硅烷基、磺酰基或膦酸基，所述方法包括将式为##STR3##的二硫杂环丙酮衍生物与式为R.sup.3 SO.sub.2 SR.sup.9 (VII)的化合物反应，其中R.sup.3和R.sup.9如上所定义的取代或未取代的含氮芳杂环残基。

  公开号：

  US04740596A1

文献信息

• Process for the preparation of 2-amino-6-nitrobenzothiazole
  申请人：Eastman Kodak Company

  公开号：US04447617A1

  公开（公告）日：1984-05-08

  Disclosed is a novel process for the preparation of 2-amino-6-nitrobenzothiazole which comprises contacting 2-mercapto-6-nitrobenzothiazole with hydrogen peroxide in the presence of ammonia. The reaction is conveniently conducted in an aqueous medium. The mole ratio of hydrogen peroxide to mercaptan is preferably about 4:1 and the reaction is conducted at a temperature of about 50.degree. to 100.degree. C.

  本发明公开了一种制备2-氨基-6-硝基苯并噻唑的新工艺，包括在氨的存在下，将2-巯基-6-硝基苯并噻唑与双氧水接触。该反应方便地在水介质中进行。双氧水与巯基的摩尔比最好为4:1，反应温度为约50℃至100℃。
• Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes
  作者：Yi-xiang Xu、Yun-yuan Huang、Rong-rong Song、Yan-liang Ren、Xin Chen、Chao Zhang、Fei Mao、Xiao-kang Li、Jin Zhu、Shuai-shuai Ni、Jian Wan、Jian Li

  DOI：10.1016/j.ejmech.2020.112500

  日期：2020.10

  Fructose-1,6-bisphosphatase (FBPase), as a key rate-limiting enzyme in the gluconeogenesis (GNG) pathway, represents a practical therapeutic strategy for type 2 diabetes (T2D). Our previous work first identified cysteine residue 128 (C128) was an important allosteric site in the structure of FBPase, while pharmacologically targeting C128 attenuated the catalytic ability of FBPase. Herein, ten approved cysteine covalent drugs were selected for exploring FBPase inhibitory activities, and the alcohol deterrent disulfiram displayed superior inhibitory efficacy among those drugs. Based on the structure of lead compound disulfiram, 58 disulfide-derived compounds were designed and synthesized for investigating FBPase inhibitory activities. Optimal compound 3a exhibited significant FBPase inhibition and glucose-lowering efficacy in vitro and in vivo. Furthermore, 3a covalently modified the C128 site, and then regulated the N125-S124-S123 allosteric pathway of FBPase in mechanism. In summary, 3a has the potential to be a novel FBPase inhibitor for T2D therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Preparation of thiocarbamyl thiazyl monosulfides
  申请人：WINGFOOT CORP

  公开号：US02615893A1

  公开（公告）日：1952-10-28
• Takahashi; Numata, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1946, vol. 66, p. Ausg. B, S. 75
  作者：Takahashi、Numata

  DOI：——

  日期：——
• Martin,D., Journal fur praktische Chemie (Leipzig 1954), 1963, vol. 19, p. 222 - 228
  作者：Martin,D.

  DOI：——

  日期：——