5-isothiocyanatoisoindoline-1,3-dione | 251576-79-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-isothiocyanatoisoindoline-1,3-dione
• 英文别名: 5-Isothiocyanato-1H-isoindole-1,3(2H)-dione；5-isothiocyanatoisoindole-1,3-dione
• CAS: 251576-79-1
• 化学式: C₉H₄N₂O₂S
• 分子量: 204.209
• InChiKey: DESTVWDPIUHLPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-isothiocyanatoisoindoline-1,3-dione 在 三乙基硅烷 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(3-(1,3-dioxoisoindolin-5-yl)thioureido)-N-hydroxybutanamide
  参考文献：
  名称：

  Discovery of the First-in-Class GSK-3β/HDAC Dual Inhibitor as Disease-Modifying Agent To Combat Alzheimer’s Disease

  摘要：

  Several evidence pointed out the role of epigenetics in Alzheimer's disease (AD) revealing strictly relationships between epigenetic and "classical" AD targets. Based on the reported connection among histone deacetylases (HDACs) and glycogen synthase kinase 3 beta (GSK-3 beta), herein we present the discovery and the biochemical characterization of the first-in-class hit compound able to exert promising anti AD effects by modulating the targeted proteins in the low micromolar range of concentration. Compound 11 induces an increase in histone acetylation and a reduction of tau phosphorylation. It is nontoxic and protective against H2O2 and 6-OHDA stimuli in SH-SY5Y and in CGN cell lines, respectively. Moreover, it promotes neurogenesis and displays immunomodulatory effects. Compound 11 shows no lethality in a wt-zebrafish model (<100 mu M) and high water solubility.

  DOI：

  10.1021/acsmedchemlett.8b00507
• 作为产物：
  描述：

  邻苯二甲酸亚胺 、 1,1′-硫代羰基二-2(1H)-吡啶酮 以 二氯甲烷 为溶剂， 以71%的产率得到5-isothiocyanatoisoindoline-1,3-dione
  参考文献：
  名称：

  Discovery of the First-in-Class GSK-3β/HDAC Dual Inhibitor as Disease-Modifying Agent To Combat Alzheimer’s Disease

  摘要：

  Several evidence pointed out the role of epigenetics in Alzheimer's disease (AD) revealing strictly relationships between epigenetic and "classical" AD targets. Based on the reported connection among histone deacetylases (HDACs) and glycogen synthase kinase 3 beta (GSK-3 beta), herein we present the discovery and the biochemical characterization of the first-in-class hit compound able to exert promising anti AD effects by modulating the targeted proteins in the low micromolar range of concentration. Compound 11 induces an increase in histone acetylation and a reduction of tau phosphorylation. It is nontoxic and protective against H2O2 and 6-OHDA stimuli in SH-SY5Y and in CGN cell lines, respectively. Moreover, it promotes neurogenesis and displays immunomodulatory effects. Compound 11 shows no lethality in a wt-zebrafish model (<100 mu M) and high water solubility.

  DOI：

  10.1021/acsmedchemlett.8b00507

文献信息

• Discovery of the First-in-Class GSK-3β/HDAC Dual Inhibitor as Disease-Modifying Agent To Combat Alzheimer’s Disease
  作者：Angela De Simone、Valeria La Pietra、Nibal Betari、Nicola Petragnani、Mariarosaria Conte、Simona Daniele、Deborah Pietrobono、Claudia Martini、Sabrina Petralla、Raffaella Casadei、Lara Davani、Flavia Frabetti、Pasquale Russomanno、Ettore Novellino、Serena Montanari、Vincenzo Tumiatti、Patrizia Ballerini、Federica Sarno、Angela Nebbioso、Lucia Altucci、Barbara Monti、Vincenza Andrisano、Andrea Milelli

  DOI：10.1021/acsmedchemlett.8b00507

  日期：2019.4.11

  Several evidence pointed out the role of epigenetics in Alzheimer's disease (AD) revealing strictly relationships between epigenetic and "classical" AD targets. Based on the reported connection among histone deacetylases (HDACs) and glycogen synthase kinase 3 beta (GSK-3 beta), herein we present the discovery and the biochemical characterization of the first-in-class hit compound able to exert promising anti AD effects by modulating the targeted proteins in the low micromolar range of concentration. Compound 11 induces an increase in histone acetylation and a reduction of tau phosphorylation. It is nontoxic and protective against H2O2 and 6-OHDA stimuli in SH-SY5Y and in CGN cell lines, respectively. Moreover, it promotes neurogenesis and displays immunomodulatory effects. Compound 11 shows no lethality in a wt-zebrafish model (<100 mu M) and high water solubility.