二氟(十一氟环己基)甲基)十七氟十氢萘 | 146931-12-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 二氟(十一氟环己基)甲基)十七氟十氢萘
• 英文名称: 4-Piperidinecarboxylic acid, 1,1'-(dithiodicarbonothioyl)bis-
• 英文别名: 1-[(4-carboxypiperidine-1-carbothioyl)disulfanyl]carbothioylpiperidine-4-carboxylic acid
• CAS: 146931-12-6
• 化学式: C₁₄H₂₀N₂O₄S₄
• 分子量: 408.588
• InChiKey: YSPRXHVWQJWIQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  196
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  二硫化碳 、 4-哌啶甲酸 在 potassium hydroxide 、 碘 作用下， 以 四氢呋喃 、 水 、 甲醇 为溶剂， 反应 13.0h， 以65%的产率得到二氟(十一氟环己基)甲基)十七氟十氢萘
  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