S-甲基-N,N-二乙基硫代氨基甲酸酯砜 | 155514-79-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 磺酰类
• 中文名称: S-甲基-N,N-二乙基硫代氨基甲酸酯砜
• 中文别名: S-甲基-N,N-二乙基硫代氨基甲酸酯砜（MeDTC）；1,5-BIS-(1,3-苯二恶酚-5-基)-3-戊二烯酮
• 英文名称: S-methyl N,N-diethylthiolcarbamate sulfone
• 英文别名: S-methyl N,N-diethylthiocarbamate sulfone；S-methyl-N,N-diethylthiocarbamate sulfone；N,N-diethylthiocarbamate methyl sulfone；N,N-diethyl-1-methylsulfonylformamide
• CAS: 155514-79-7
• 化学式: C₆H₁₃NO₃S
• 分子量: 179.24
• InChiKey: XRFGLFAEBISDIV-UHFFFAOYSA-N

物化性质

• 沸点：
  259.3±23.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319
• 储存条件：
  存储条件：2-8°C，密封保存，置于干燥处。

制备方法与用途

MeDTC（S-甲基-N,N-二乙基硫代氨基甲酸砜）是二硫仑的代谢产物，是一种高效的不可逆醛脱氢酶（ALDH）抑制剂。

反应信息

• 作为反应物：
  描述：

  N-乙酰-L-半胱氨酸 、 S-甲基-N,N-二乙基硫代氨基甲酸酯砜 以 phosphate buffer 为溶剂， 生成 N-acetyl-S-(N,N-diethylcarbamoyl)cysteine
  参考文献：
  名称：

  Hu, Pei; Jin, Lixia; Baillie, Thomas A., Journal of Pharmacology and Experimental Therapeutics, 1997, vol. 281, # 2, p. 611 - 617

  摘要：

  DOI：
• 作为产物：
  描述：

  S-甲基 N,N-二乙基硫代氨基甲酸酯 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以65%的产率得到S-甲基-N,N-二乙基硫代氨基甲酸酯砜
  参考文献：
  名称：

  S-甲基N，N-二乙基硫代氨基甲酸酯砜，双硫仑的潜在代谢产物和低Km线粒体醛脱氢酶的强效抑制剂

  摘要：

  双硫仑抑制肝醛脱氢酶（ALDH），导致乙醇摄入后乙醛积聚。据认为，双硫仑在体内的寿命太短而不能直接抑制ALDH，而是被生物转化为抑制该酶的反应性代谢产物。N-N，N-二乙基硫代氨基甲酸酯的S-甲基（MeDTC）亚砜已在给予双硫仑的动物的血液中鉴定出来，并且是ALDH的有效抑制剂（Hart和Faiman，Biochem Pharmacol 46：2285-2290，1993）。MeDTC砜是MeDTC亚砜的逻辑代谢产物。因此，我们研究了MeDTC砜对大鼠肝低Km线粒体ALDH（乙醛代谢中的主要酶）的活性的影响。与双硫仑相比，MeDTC砜在体外抑制低Km线粒体ALDH的IC50为0.42 +/- 0.04 microM（平均+/- SD，N = 5），在相同条件下的IC50为7.5 +/- 1.2 microM。MeDTC砜对ALDH的抑制作用是时间依赖性的。在0.6 microM MeDTC

  DOI：

  10.1016/0006-2952(94)00504-f

文献信息

• Disulfiram Generates a Stable <i>N</i>,<i>N</i>-Diethylcarbamoyl Adduct on Cys-125 of Rat Hemoglobin β-Chains in Vivo
  作者：John C. L. Erve、Ole N. Jensen、Holly S. Valentine、Venkataraman Amarnath、William M. Valentine

  DOI：10.1021/tx990191n

  日期：2000.4.1

  the DSF metabolite S-methyl-N, N-diethylthiocarbamate sulfoxide reacts irreversibly with an active site Cys. This work aimed to determine if DSF generates monothiocarbamate adducts on cysteine residues in vivo by examining hemoglobin. Sprague-Dawley rats were treated with DSF po for 2, 4, and 6 weeks. Rats have four different globin beta-chains, of which three (beta-1-3) contain two cysteine residues

  双硫仑（DSF）是一种用于厌恶疗法的药物，用于治疗酒精中毒，并通过抑制线粒体低K（m）醛脱氢酶起作用。对体内失活机理的研究表明，DSF代谢产物S-甲基-N，N-二乙基硫代氨基甲酸酯亚砜与活性位点Cys不可逆地反应。这项工作旨在通过检查血红蛋白来确定DSF是否在体内半胱氨酸残基上生成单硫代氨基甲酸酯加合物。用DSF po处理Sprague-Dawley大鼠2、4和6周。大鼠具有4条不同的球蛋白β链，其中3条（β-1-3）各自包含2个半胱氨酸残基。通过HPLC收集的来自DSF处理的大鼠的两种新球蛋白的MALDI-TOF MS分析显示，未修饰链（β-2和β-3）的质量增加了99 Da。在另一个实验中 将球蛋白混合物用Glu-C消化2 h，然后用MALDI-TOF MS重新分析。结果显示，m / z 2716.3的肽质量比已知的含Cys肽高99 Da。随后，使用Q-TOF串联质谱分析了Glu-C消化物，从而可以通过m
• Agent for controlling cells constituting cancer microenvironment or inflammatory microenvironment
  申请人：The University of Tokyo

  公开号：US10722480B2

  公开（公告）日：2020-07-28

  An agent according to the present invention comprises as an effective component any of (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate; (2) a pharmaceutically acceptable salt of (1); or (3) a solvate of (1) or (2), and is used for inhibition of interaction between CR2B or CCR5 and FROUNT protein, inhibition of macrophages, control of cells constituting a cancer microenvironment or inflammatory microenvironment, or enhancement of anticancer activity of an anticancer drug. It is also possible to provide a compound with a reduced side effect and an increased pharmacological effect by identifying a disulfiram derivative having a lower aldehyde dehydrogenase-inhibiting activity and a higher FROUNT-inhibiting activity among derivatives prepared by structural modification of disulfiram.

  根据本发明的制剂包括作为有效成分的(1)双硫仑、二乙基二硫代氨基甲酸二乙酯或二乙基二硫代氨基甲酸二乙酯的金属络合物；(2)(1)的药学上可接受的盐；或 (3) (1) 或 (2) 的溶解物，用于抑制 CR2B 或 CCR5 与 FROUNT 蛋白之间的相互作用，抑制巨噬细胞，控制构成癌症微环境或炎症微环境的细胞，或增强抗癌药物的抗癌活性。此外，还可以通过在通过对双硫仑进行结构修饰制备的衍生物中找出一种具有较低醛脱氢酶抑制活性和较高 FROUNT 抑制活性的双硫仑衍生物，从而提供一种副作用较小而药理作用较强的化合物。
• Therapeutic compositions
  申请人：Schloss V. John

  公开号：US20050130904A1

  公开（公告）日：2005-06-16

  A method is provided for the preparation of compounds of the formula (R 1 )(R 2 )NC(═X)S(O) n R 3 or (R 1 )(R 2 )NC(═X)OS(O) n R 3 , wherein R 1 , R 2 and R 3 , X and n have any of the meanings defined in the specification. A method is also provided for the detection and quantitation of compounds of the formula (R 1 )(R 2 )NC(═X)OS(O) n R 3 . A method to link a therapeutic agent to a compound that is conjugated to glutathione is also provided for the purpose of improving the therapeutic properties of the therapeutic agent. Novel compounds, intermediates, pharmaceutical compositions and methods of use are also provided.

  提供了一种制备式（R 1 )(R 2 )NC(═X)S(O) n R 3 或（R 1 )(R 2 )NC(═X)OS(O) n R 3 其中 R 1 , R 2 和 R 3 X 和 n 具有说明书中定义的任何含义。还提供了一种检测和定量式（R 1 )(R 2 NC(═X)OS(O) n R 3 .为了改善治疗剂的治疗特性，还提供了一种将治疗剂与谷胱甘肽共轭的化合物连接的方法。还提供了新型化合物、中间体、药物组合物和使用方法。
• Glutathione Carbamoylation with S-Methyl N,N-diethylthiolcarbamate Sulfoxide and Sulfone
  作者：Nagendra S Ningaraj、John V Schloss、Todd D Williams、Morris D Faiman

  DOI：10.1016/s0006-2952(97)00513-3

  日期：1998.3

  S-Methyl N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO) and sulfone (DETC-MeSO2) both inhibit rat liver low K-m aldehyde dehydrogenase (ALDH(2)) in vitro and in vivo (Nagendra et al., Biochem Pharmacol 47: 1465-1467, 1994). DETC-MeSO has been shown to be a metabolite of disulfiram, but DETC-MeSO2 has not. Studies were carried out to further investigate the inhibition of ALDH(2) by DETC-MeSO and DETC-MeSO2. In an in vitro system containing hydrogen peroxide and horseradish peroxidase, the rate of DETC-MeSO oxidation corresponded to the rate of DETC-MeSO2 formation. Carbamoylation of GSH by both DETC-MeSO and DETC-MeSO2 was observed in a rat liver S-9 fraction. Carbamoylation of GSH was not observed in the presence of N-methylmaleimide. In in vitro studies, DETC-MeSO and DETC-MeSO2 were equipotent ALDH(2) inhibitors when solubilized mitochondria were used, but DETC-MeSO was approximately four times more potent than DETC-MeSO2 in intact mitochondria. In studies with rats, the dose (i.p. or oral) required to inhibit 50% ALDH(2) (ED50) was 3.5 mg/kg for DETC-MeSO and approximately 35 mg/kg for DETC-MeSO2, approximately a 10-fold difference. Furthermore, maximum ALDH(2) inhibition occurred 1 hr after DETC-MeSO administration, whereas maximal ALDH(2) inhibition occurred 8 hr after DETC-MeSO2 dosing. DETC-MeSO is, therefore, not only a more potent ALDH(2) inhibitor than DETC-MeSO2 in vivo, but also in vitro when intact mitochondria are utilized. The in vitro results thus support the in vivo findings. Since oxidation of DETC-MeSO can occur both enzymatically and non-enzymatically, it is possible that DETC-MeSO2 is formed in vivo. DETC-MeSO2, however, is not as effective as DETC-MeSO in inhibiting ALDH(2), probably because it has difficulty penetrating the mitochondrial membrane. Thus, even if DETC-MeSO2 is formed in vivo from DETC-MeSO, it is the metabolite DETC-MeSO that is most likely responsible for the inhibition of ALDH(2) after disulfiram administration. (C) 1998 Elsevier Science Inc.
• AGENT FOR CONTROLLING CELLS CONSTITUTING CANCER MICROENVIRONMENT OR INFLAMMATORY MICROENVIRONMENT
  申请人：The University of Tokyo

  公开号：US20180000755A1

  公开（公告）日：2018-01-04

  An agent according to the present invention comprises as an effective component any of (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate; (2) a pharmaceutically acceptable salt of (1); or (3) a solvate of (1) or (2), and is used for inhibition of interaction between CR2B or CCR5 and FROUNT protein, inhibition of macrophages, control of cells constituting a cancer microenvironment or inflammatory microenvironment, or enhancement of anticancer activity of an anticancer drug. It is also possible to provide a compound with a reduced side effect and an increased pharmacological effect by identifying a disulfiram derivative having a lower aldehyde dehydrogenase-inhibiting activity and a higher FROUNT-inhibiting activity among derivatives prepared by structural modification of disulfiram.