3-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indol-7-yl]propionic acid ethyl ester | 1141334-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indol-7-yl]propionic acid ethyl ester
• 英文别名: ethyl 3-[3-[4-(1-benzofuran-3-yl)-2,5-dioxopyrrol-3-yl]-1-methylindol-7-yl]propanoate
• CAS: 1141334-03-3
• 化学式: C₂₆H₂₂N₂O₅
• 分子量: 442.471
• InChiKey: NTBZBLYGADQZHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  90.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indol-7-yl]propionic acid ethyl ester 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以39%的产率得到3-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indol-7-yl]propionic acid
  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-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1Hpyrrol-3-yl)-1-methyl-1H-indol-7-yl]acrylic acid ethyl ester 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.25h， 以45%的产率得到3-[3-(4-benzofuran-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-methyl-1H-indol-7-yl]propionic 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