bis(3,4-dihydroquinoline-1(2H)-yl-thiocarbonyl)disulfide | 1196834-70-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: bis(3,4-dihydroquinoline-1(2H)-yl-thiocarbonyl)disulfide
• 英文别名: bis(1,2,3,4-tetrahydroquinolin-1-ylthiocarbonyl)disulfide；Bis(1,2,3,4-tetrahydroquinoline-1-thiocarbonyl) disulfide；3,4-dihydro-2H-quinoline-1-carbothioylsulfanyl 3,4-dihydro-2H-quinoline-1-carbodithioate
• CAS: 1196834-70-4
• 化学式: C₂₀H₂₀N₂S₄
• 分子量: 416.656
• InChiKey: JWLSRLDWCJQHAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  吲哚 、 bis(3,4-dihydroquinoline-1(2H)-yl-thiocarbonyl)disulfide 在 potassium tert-butylate 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以73%的产率得到1H-indol-1-yl 3,4-dihydroquinoline-1(2H)-carbodithioate
  参考文献：
  名称：

  碱促进合成新型吲哚-二硫代氨基甲酸酯化合物，作为治疗急性肺损伤的潜在消炎药

  摘要：

  通过使用t- BuOK作为促进剂，实现了具有高化学选择性地将二硫代氨基甲酸酯基团引入到带有双（二烷基胺硫代羰基）二硫化物的吲哚氮位置的有效方案。基于这种方法，在室温下以中等至极好的收率制备了29种新颖的吲哚-二硫代氨基甲酸酯化合物。评价所有化合物的抗炎活性。大多数化合物在抑制肿瘤坏死因子α（TNF-α）和白介素6（IL-6）释放方面显示出高效力。发现其中四个以剂量依赖性方式抑制玻璃体细胞因子的产生，IC 50值在纳摩尔范围内。此外，3-甲基-1H-吲哚-1-基二甲基氨基甲二硫代吲哚（3o）有效改善了肺组织的组织病理学变化，并减轻了脂多糖（LPS）诱导的体内急性肺损伤（ALI）。这些数据表明，新的吲哚-二硫代氨基甲酸酯衍生物可能对进一步治疗ALI的药物开发特别有用。

  DOI：

  10.1016/j.ejmech.2019.03.022
• 作为产物：
  描述：

  potassium;3,4-dihydro-2H-quinoline-1-carbodithioate 在 盐酸 、 sodium nitrite 作用下， 以 甲醇 、 水 为溶剂， 生成 bis(3,4-dihydroquinoline-1(2H)-yl-thiocarbonyl)disulfide
  参考文献：
  名称：

  Bis(dialkylaminethiocarbonyl)disulfides as Potent and Selective Monoglyceride Lipase Inhibitors

  摘要：

  Monoglyceride lipase (MGL) inhibition may offer an approach in treating diseases in which higher 2-arachidonoyglycerol activity would be beneficial. We report here the synthesis and pharmacological evaluation of bis(dialkylaminethiocarbonyl)disulfide derivatives as irreversible MGL inhibitors. Inhibition occurs through interactions with MGL C208 and C242 residues, and these derivatives exhibit high inhibition selectivity over fatty acid amide hydrolase, another endocannabinoid-hydrolyzing enzyme.

  DOI：

  10.1021/jm901323s

文献信息

• 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.
• Bis(dialkylaminethiocarbonyl)disulfides as Potent and Selective Monoglyceride Lipase Inhibitors
  作者：Coco N. Kapanda、Giulio G. Muccioli、Geoffray Labar、Jacques H. Poupaert、Didier M. Lambert

  DOI：10.1021/jm901323s

  日期：2009.11.26

  Monoglyceride lipase (MGL) inhibition may offer an approach in treating diseases in which higher 2-arachidonoyglycerol activity would be beneficial. We report here the synthesis and pharmacological evaluation of bis(dialkylaminethiocarbonyl)disulfide derivatives as irreversible MGL inhibitors. Inhibition occurs through interactions with MGL C208 and C242 residues, and these derivatives exhibit high inhibition selectivity over fatty acid amide hydrolase, another endocannabinoid-hydrolyzing enzyme.
• Base promoted synthesis of novel indole-dithiocarbamate compounds as potential anti-inflammatory therapeutic agents for treatment of acute lung injury
  作者：Zengqiang Song、Yan Zhou、Wenxin Zhang、Lingling Zhan、Yuanzu Yu、Yuehui Chen、Wenjing Jia、Zhiguo Liu、Jianchang Qian、Yali Zhang、Chenglong Li、Guang Liang

  DOI：10.1016/j.ejmech.2019.03.022

  日期：2019.6

  Additionally, 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o) effectively ameliorated histopathological changes of lung tissues and attenuated lipopolysaccharides (LPS)-induced acute lung injury (ALI) in vivo. These data suggest that the new indole-dithiocarbamate derivatives could be particularly useful for further pharmaceutical development for the treatment of ALI.

  通过使用t- BuOK作为促进剂，实现了具有高化学选择性地将二硫代氨基甲酸酯基团引入到带有双（二烷基胺硫代羰基）二硫化物的吲哚氮位置的有效方案。基于这种方法，在室温下以中等至极好的收率制备了29种新颖的吲哚-二硫代氨基甲酸酯化合物。评价所有化合物的抗炎活性。大多数化合物在抑制肿瘤坏死因子α（TNF-α）和白介素6（IL-6）释放方面显示出高效力。发现其中四个以剂量依赖性方式抑制玻璃体细胞因子的产生，IC 50值在纳摩尔范围内。此外，3-甲基-1H-吲哚-1-基二甲基氨基甲二硫代吲哚（3o）有效改善了肺组织的组织病理学变化，并减轻了脂多糖（LPS）诱导的体内急性肺损伤（ALI）。这些数据表明，新的吲哚-二硫代氨基甲酸酯衍生物可能对进一步治疗ALI的药物开发特别有用。