N,N-二乙基-1-甲基亚磺酰甲酰胺 | 140703-15-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 亚砜
• 中文名称: N,N-二乙基-1-甲基亚磺酰甲酰胺
• 中文别名: 2-丙烯酸,2-甲基-,十二基酯,聚合二十烷基2-甲基-2-丙烯酸酯,十六烷基2-甲基-2-丙烯酸酯,十八烷基2-甲基-2-丙烯酸酯和十四烷基2-甲基-2-丙烯酸酯
• 英文名称: methyl diethylthiocarbamoyl-sulfoxide
• 英文别名: S-methyl N,N-diethylthiocarbamate sulfoxide；S-Methyl-N,N-diethylthiocarbamoyl sulfoxide；S-methyl-N, N-diethylthiolcarbamate sulfoxide；N,N-diethyl-1-methylsulfinylformamide
• CAS: 140703-15-7
• 化学式: C₆H₁₃NO₂S
• 分子量: 163.241
• InChiKey: FQSRGOGWCPXJIN-UHFFFAOYSA-N

物化性质

• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 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：
  56.6
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

MeDTC亚砜是S-甲基二乙基硫代氨基甲酸酯的人类已知代谢物。

MeDTC sulfoxide is a known human metabolite of s-methyl diethylthiocarbamate.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  N,N-二乙基-1-甲基亚磺酰甲酰胺 在 双氧水 、 horse radish peroxidase 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 S-甲基-N,N-二乙基硫代氨基甲酸酯砜
  参考文献：
  名称：

  Glutathione Carbamoylation with S-Methyl N,N-diethylthiolcarbamate Sulfoxide and Sulfone

  摘要：

  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.

  DOI：

  10.1016/s0006-2952(97)00513-3
• 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， 反应 1.0h， 生成 N,N-二乙基-1-甲基亚磺酰甲酰胺
  参考文献：
  名称：

  双硫仑和二硫代氨基甲酸酯类似物具有良好的抗血吸虫作用

  摘要：

  血吸虫病是一种被忽视的热带疾病，每年有超过 2 亿新感染病例。它是由血吸虫属的寄生虫引起的如果不及时治疗，可能会导致死亡。目前，只有两种药物可用于对抗血吸虫病：吡喹酮和在有限范围内的奥沙尼喹。然而，这两种药物的密集使用导致出现耐药性的可能性增加。因此，必须寻找新的活性物质并进行有针对性的开发。在这项研究中，强调了“二硫代氨基甲酸盐”物质类别及其作为抗血吸虫剂的潜力。这些化合物来源于人醛脱氢酶抑制剂双硫仑（四乙基秋兰姆二硫化物，DSF）及其代谢物的基本结构。我们的化合物对曼氏血吸虫成虫显示出有希望的活性（体外）。，如产蛋量减少、配对稳定性、活力和运动性。此外，观察到外皮损伤以及肠道扩张甚至寄生虫死亡。我们对二硫代氨基甲酸酯核心的两侧进行了详细的结构-活性关系研究，产生了大约 300 种衍生物的库（此处显示了 116 种衍生物）。从 100 μ m开始，我们将抗血吸虫活性提高到25 μ m例如

  DOI：

  10.1016/j.ejmech.2022.114641

文献信息

• S-Methyl N,N-diethylthiocarbamate sulfone, a potential metabolite of disulfiram and potent inhibitor of low Km mitochondrial aldehyde dehydrogenase
  作者：Dennis C. Mays、Albert N. Nelson、Abdul H. Fauq、Zachary H. Shriver、Karen A. Veverka、Stephen Naylor、James J. Lipsky

  DOI：10.1016/0006-2952(94)00504-f

  日期：1995.3

  Disulfiram inhibits hepatic aldehyde dehydrogenase (ALDH) causing an accumulation of acetaldehyde after ethanol ingestion. It is thought that disulfiram is too short-lived in vivo to directly inhibit ALDH, but instead is biotransformed to reactive metabolites that inhibit the enzyme. S-Methyl N,N-diethylthiocarbamate (MeDTC) sulfoxide has been identified in the blood of animals given disulfiram and

  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
• Method for treatment of glutamate related disorders
  申请人：——

  公开号：US20010031730A1

  公开（公告）日：2001-10-18

  Disclosed are novel compounds and novel pharmaceutical compositions for use in medical therapy, as well as intermediates and processes for preparing such compounds. Therapeutic methods for preventing or treating glutamate-related disorders in a mammal and methods to inhibit or prevent glutamate binding in mammalian tissue are also disclosed.

  本发明涉及新型化合物和新型药物组合物，用于医疗治疗，以及制备这些化合物的中间体和过程。还公开了在哺乳动物中预防或治疗谷氨酸相关疾病的治疗方法，以及抑制或预防哺乳动物组织中谷氨酸结合的方法。
• [EN] COMPOUNDS AND METHODS FOR TREATING ALCOHOL USE DISORDER<br/>[FR] COMPOSES ET MÉTHODES DE TRAITEMENT D'UN TROUBLE LIÉ À LA CONSOMMATION D'ALCOOL
  申请人：FELDBERG LEWIS

  公开号：WO2022115742A1

  公开（公告）日：2022-06-02

  The disclosure is directed to, in part, compounds, or pharmaceutically acceptable salts or solvates thereof, for modulating the activity of aldehyde dehydrogenase such as ALDH2 and/or methods for treating and/or preventing an alcohol related disorder such as alcohol use disorder, alcohol induced disorder, alcohol abuse, alcohol dependence, alcohol intoxication, alcohol withdrawal, and the like and/or methods for reducing the amount of alcohol consumed, reducing alcoholic cravings, or increasing the percentage of no heavy drinking days for a subject with alcohol use disorder.

  该披露涉及部分化合物或其药学上可接受的盐或溶剂，用于调节醛脱氢酶如ALDH2的活性，以及/或治疗和/或预防与酒精相关的障碍，如酒精使用障碍、酒精引起的障碍、酒精滥用、酒精依赖、酒精中毒、酒精戒断等，以及/或减少饮酒量、减少对酒精的渴求或增加患有酒精使用障碍者的无重度饮酒日的百分比的方法。
• Thiocarbamate sulfoxide composition for deterring ethanol ingestion
  申请人：Faiman, Morris D.

  公开号：EP1216703A2

  公开（公告）日：2002-06-26

  A method is provided for deterring ethanol ingestion by a human, comprising administering to said human an amount of a compound of the formula (R1)(R2)NC(X)S(O)R3 effective to cause the disulfiramethanol reaction in said human, wherein R1, R2 and R3 are each (C1-C4) alkyl groups, e.g., methyl, ethyl, propyl, isopropyl, butyl, i-butyl and t-butyl.

  提供了一种阻止人类摄入乙醇的方法，该方法包括向所述人类施用一定量的式(R1)(R2)NC(X)S(O)R3化合物，该化合物能有效地在所述人类体内引起二硫代甲醇反应，其中R1、R2和R3各自为(C1-C4)烷基，例如甲基、乙基、丙基、异丙基、丁基、i-丁基和t-丁基。
• KETAMINE FORMULATIONS
  申请人：Otonomy, Inc.

  公开号：EP2932971A1

  公开（公告）日：2015-10-21

  Formulations of ketamine for administration to the inner or middle ear.

  用于内耳或中耳给药的氯胺酮制剂。