3-(benzofuran-3-yl)-4-(5-bromo-1-methyl-1H-pyrrolo[2,3-b]-pyridin-3-yl)-1H-pyrrole-2,5-dione | 1443411-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 3-(benzofuran-3-yl)-4-(5-bromo-1-methyl-1H-pyrrolo[2,3-b]-pyridin-3-yl)-1H-pyrrole-2,5-dione
• 英文别名: 3-(1-Benzofuran-3-yl)-4-(5-bromo-1-methylpyrrolo[2,3-b]pyridin-3-yl)pyrrole-2,5-dione；3-(1-benzofuran-3-yl)-4-(5-bromo-1-methylpyrrolo[2,3-b]pyridin-3-yl)pyrrole-2,5-dione
• CAS: 1443411-12-8
• 化学式: C₂₀H₁₂BrN₃O₃
• 分子量: 422.238
• InChiKey: SBXZEXINQCGSMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴-1-甲基-1H-吡咯并[2,3-b]吡啶 在 aluminum (III) chloride 、 potassium tert-butylate 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 3-(benzofuran-3-yl)-4-(5-bromo-1-methyl-1H-pyrrolo[2,3-b]-pyridin-3-yl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Characterization of Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as Stimulators of Steroidogenesis

  摘要：

  Inhibition of GSK-3 beta has been well documented to account for the behavioral actions of the mood stabilizer lithium in various animal models of mood disorders. Recent studies have showed that genetic or pharmacological inhibition of GSK-3 beta resulted in anxiolytic-like and pro-social behavior. In our ongoing efforts to develop GSK-3 beta inhibitors for the treatment of mood disorders, SAR studies on maleimide-based compounds were undertaken. We present herein for the first time that some of these GSK-3 beta inhibitors, in particular analogues 1 and 9, were able to stimulate progesterone production in the MA-10 mouse tumor Leydig cell model of steroidogenesis without any significant toxicity. These two compounds were tested in the SmartCube behavioral assay and showed anxiolytic-like signatures following daily dose administration (50 mg/kg, ip) for 13 days. Taken together, these results support the hypothesis that GSK-3 beta inhibition could influence neuroactive steroid production thereby mediating the modulation of anxiety-like behavior in vivo.

  DOI：

  10.1021/jm400511s

文献信息

• Characterization of Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as Stimulators of Steroidogenesis
  作者：Hendra Gunosewoyo、Andrew Midzak、Irina N. Gaisina、Emily V. Sabath、Allison Fedolak、Taleen Hanania、Dani Brunner、Vassilios Papadopoulos、Alan P. Kozikowski

  DOI：10.1021/jm400511s

  日期：2013.6.27

  Inhibition of GSK-3 beta has been well documented to account for the behavioral actions of the mood stabilizer lithium in various animal models of mood disorders. Recent studies have showed that genetic or pharmacological inhibition of GSK-3 beta resulted in anxiolytic-like and pro-social behavior. In our ongoing efforts to develop GSK-3 beta inhibitors for the treatment of mood disorders, SAR studies on maleimide-based compounds were undertaken. We present herein for the first time that some of these GSK-3 beta inhibitors, in particular analogues 1 and 9, were able to stimulate progesterone production in the MA-10 mouse tumor Leydig cell model of steroidogenesis without any significant toxicity. These two compounds were tested in the SmartCube behavioral assay and showed anxiolytic-like signatures following daily dose administration (50 mg/kg, ip) for 13 days. Taken together, these results support the hypothesis that GSK-3 beta inhibition could influence neuroactive steroid production thereby mediating the modulation of anxiety-like behavior in vivo.