2-(diethylamino)-2-thioxoethyl diethylcarbamodithioate | 120508-37-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫代酰胺
• 英文名称: 2-(diethylamino)-2-thioxoethyl diethylcarbamodithioate
• 英文别名: (Diethylthiocarbamoyl)methylene diethylcarbamodithioate；[2-(diethylamino)-2-sulfanylideneethyl] N,N-diethylcarbamodithioate
• CAS: 120508-37-4
• 化学式: C₁₁H₂₂N₂S₃
• 分子量: 278.507
• InChiKey: CNCIYWYBJUTHQW-UHFFFAOYSA-N

物化性质

• 熔点：
  57-58 °C
• 沸点：
  347.2±52.0 °C(Predicted)
• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  96
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(diethylamino)-2-oxoethyl diethylcarbamodithioate 在 P₂S₅/alumina 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 2-(diethylamino)-2-thioxoethyl diethylcarbamodithioate
  参考文献：
  名称：

  Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2020.112500

文献信息

• 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.
• Kuliev, A. B.; Dzhavadov, M. M.; Abushova, B. A., Journal of applied chemistry of the USSR, 1988, vol. 61, # 6, p. 1246 - 1249
  作者：Kuliev, A. B.、Dzhavadov, M. M.、Abushova, B. A.

  DOI：——

  日期：——
• 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.