butyl diethylcarbamo(dithioperoxo)thioate | 22718-34-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 有机二硫化物
• 英文名称: butyl diethylcarbamo(dithioperoxo)thioate
• 英文别名: butylsulfanyl N,N-diethylcarbamodithioate
• CAS: 22718-34-9
• 化学式: C₉H₁₉NS₃
• 分子量: 237.455
• InChiKey: PCMFCEGDFCTXRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  85.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  二硫化四乙基秋兰姆 、 丁硫醇 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 butyl diethylcarbamo(dithioperoxo)thioate
  参考文献：
  名称：

  Pharmacological evaluation of disulfiram analogs as antimicrobial agents and their application as inhibitors of fosB-mediated fosfomycin resistance

  摘要：

  酒精戒断药物二硫仑（Antabuse®）的二硫化物类似物被评估其抗微生物活性。对耐甲氧西林金黄色葡萄球菌（MRSA）和其他致病生物的最低抑菌浓度（MIC）数据进行的结构活性关系分析显示，取代基的亲脂性和体积之间存在相关性。具有最佳抗MRSA活性的类似物含有S-辛基二硫化物和N,N-二甲基或N-吡咯烷二硫代氨基甲酸酯取代基。额外测试表明，二硫仑及其S-辛基衍生物均能使金黄色葡萄球菌对磷霉素的杀菌效果产生敏感性。机制研究表明，这些化合物通过硫醇-二硫键交换反应降低了胞内辅因子巴克利硫醇的水平。因此，金黄色葡萄球菌对磷霉素的增敏被归因于可用于fosB失活的细胞内巴克利硫醇池的耗竭。

  DOI：

  10.1038/s41429-022-00500-2

文献信息

• Exploring the Structural Requirements for Inhibition of the Ubiquitin E3 Ligase Breast Cancer Associated Protein 2 (BCA2) as a Treatment for Breast Cancer
  作者：Ghali Brahemi、Fathima R. Kona、Annalisa Fiasella、Daniela Buac、Jitka Soukupová、Andrea Brancale、Angelika M. Burger、Andrew D. Westwell

  DOI：10.1021/jm901757t

  日期：2010.4.8

  The zinc-ejecting aldehyde dehydrogenase (A LDH) inhibitory drug disulfiram (DS F) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C=S)S-S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC(50)) in BCA2 positive MCF-7 and T47D cells but were inactive (IC(50)> 10 mu M) in BCA2 negative M DA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve M DA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.
• Disulfiram-based disulfides as narrow-spectrum antibacterial agents
  作者：Jordan G. Sheppard、Keely R. Frazier、Pushkar Saralkar、Mohammad F. Hossain、Werner J. Geldenhuys、Timothy E. Long

  DOI：10.1016/j.bmcl.2018.03.023

  日期：2018.5

  Sixteen disulfides derived from disulfiram (Antabuse (TM)) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. In the final analysis, this investigation concluded that the S-octylthio derivative is a more effective growth inhibitor of Gram-positive bacteria than disulfiram and exhibits more favorable cytotoxic and metabolic parameters over disulfiram. (C) 2018 Elsevier Ltd. All rights reserved.
• [EN] ANTI-CANCER THERAPEUTIC AGENTS<br/>[FR] AGENTS THÉRAPEUTIQUES ANTICANCÉREUX
  申请人：UNIV WAYNE STATE

  公开号：WO2011097218A1

  公开（公告）日：2011-08-11

  There is provided the use of disulfiram and analogs thereof to inhibit catalytic activity. Additionally, dithioperoxothioates can be used to inhibit catalytic activity. More specifically, the present invention is utilized to inhibit the catalytic activity of ubiquitin E3 ligase BCA2 for treating cancer.
• Pharmacological evaluation of disulfiram analogs as antimicrobial agents and their application as inhibitors of fosB-mediated fosfomycin resistance
  作者：Alexandria D. Lewis、Taylor M. Riedel、Meredith B. A. Kesler、Melinda E. Varney、Timothy E. Long

  DOI：10.1038/s41429-022-00500-2

  日期：2022.3

  Disulfide analogs of the alcohol sobriety medication disulfiram (Antabuse®) were evaluated for antimicrobial activity. Structure-activity relationship analyses of MIC data obtained for methicillin-resistant Staphylococcus aureus (MRSA) and other pathogenic organisms revealed correlations between the lipophilicity and bulkiness of the substituents. Analogs conferring optimal anti-MRSA activity contained S-octyl disulfides and either N,N-dimethyl- or N-pyrrolidine dithiocarbamate substituents. Additional testing revealed that both disulfiram and its S-octyl derivative are capable of sensitizing S. aureus to the bactericidal effects of fosfomycin. Mechanistic studies established that the compounds decrease intracellular levels of the fosB cofactor bacillithiol through a thiol-disulfide exchange reaction. The increased fosfomycin susceptibility in S. aureus was thereby attributed to a depleted cellular bacillithiol pool available for inactivation by fosB.

  酒精戒断药物二硫仑（Antabuse®）的二硫化物类似物被评估其抗微生物活性。对耐甲氧西林金黄色葡萄球菌（MRSA）和其他致病生物的最低抑菌浓度（MIC）数据进行的结构活性关系分析显示，取代基的亲脂性和体积之间存在相关性。具有最佳抗MRSA活性的类似物含有S-辛基二硫化物和N,N-二甲基或N-吡咯烷二硫代氨基甲酸酯取代基。额外测试表明，二硫仑及其S-辛基衍生物均能使金黄色葡萄球菌对磷霉素的杀菌效果产生敏感性。机制研究表明，这些化合物通过硫醇-二硫键交换反应降低了胞内辅因子巴克利硫醇的水平。因此，金黄色葡萄球菌对磷霉素的增敏被归因于可用于fosB失活的细胞内巴克利硫醇池的耗竭。