3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indole-7-carbaldehyde | 1141334-57-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indole-7-carbaldehyde
• CAS: 1141334-57-7
• 化学式: C₂₂H₁₄N₂O₄
• 分子量: 370.364
• InChiKey: DMVDRYNPPSACKD-UHFFFAOYSA-N

物化性质

• 沸点：
  658.4±55.0 °C(predicted)
• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

反应信息

• 作为反应物：
  描述：

  3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indole-7-carbaldehyde 、 乙氧甲酰基亚甲基三苯基膦 以 四氢呋喃 为溶剂， 以37 mg的产率得到3-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1Hpyrrol-3-yl)-1-methyl-1H-indol-7-yl]acrylic acid ethyl ester
  参考文献：
  名称：

  From a Natural Product Lead to the Identification of Potent and Selective Benzofuran-3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3β Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells

  摘要：

  Recent studies have demonstrated that glycogen synthase kinase 3 beta (GSK-3 beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3 beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3 beta and an enhanced selectivity against cycl in-dependent kinase 2 (CDK-2). Selected GSK-3 beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3 beta inhibitors 5 and 26 resulted in suppression of GSK-3 beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3 beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.

  DOI：

  10.1021/jm801317h
• 作为产物：
  描述：

  3-benzofuran-3-yl-4-(7-hydroxymethyl-1-methyl-1H-indol-3-yl)pyrrole-2,5-dione 在 重铬酸吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indole-7-carbaldehyde
  参考文献：
  名称：

  From a Natural Product Lead to the Identification of Potent and Selective Benzofuran-3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3β Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells

  摘要：

  Recent studies have demonstrated that glycogen synthase kinase 3 beta (GSK-3 beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3 beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3 beta and an enhanced selectivity against cycl in-dependent kinase 2 (CDK-2). Selected GSK-3 beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3 beta inhibitors 5 and 26 resulted in suppression of GSK-3 beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3 beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.

  DOI：

  10.1021/jm801317h