3-(3,4,5-trimethoxyphenyl)-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indol-3-yl)-1,5-dihydro-2H-pyrrole-2-one | 1038914-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(3,4,5-trimethoxyphenyl)-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indol-3-yl)-1,5-dihydro-2H-pyrrole-2-one
• 英文别名: 3-(3,4,5-Trimethoxyphenyl)-4-(1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-indol-3-yl)-1,5-dihydro-2H-pyrrole-2-one；4-(3,4,5-trimethoxyphenyl)-3-[1-(2-trimethylsilylethoxymethyl)indol-3-yl]-1,2-dihydropyrrol-5-one
• CAS: 1038914-79-2
• 化学式: C₂₇H₃₄N₂O₅Si
• 分子量: 494.663
• InChiKey: OBFNFWMFLWGMPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.02
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3,4,5-trimethoxyphenyl)-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indol-3-yl)-1,5-dihydro-2H-pyrrole-2-one 、 异丙醇 在 盐酸 作用下， 反应 1.0h， 以83%的产率得到4-[1-(isopropoxymethyl)-1H-indol-3-yl]-3-(3,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrole-2-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel 3-Aryl-4-(1H-indole-3yl)-1,5-dihydro-2H-pyrrole-2-ones as Vascular Endothelial Growth Factor Receptor (VEGF-R) Inhibitors

  摘要：

  In this study we report on the design, synthesis, and biological evaluation of pyrrole-2-one 2 to be a highly potent VEGF-R2/3 inhibitor with IC50 of 31/37 nM. The novel 3,4-diaryl-2H-pyrrole-2-ones were designed on the basis of the modeled binding mode of the corresponding 1H-pyrrole-2,5-dione (maleimide) VEGFR2/3 inhibitor I indicating two H-bond ligand-protein interactions in the ATP pocket for the amide 2 but not for the isomer 3. Flexible synthetic routes to 3,4-diaxyl-2H-pyrrole-2-ones and structure - activity relationships for the compounds in a panel of 24 therapeutically relevant protein kinases (IC50 values) are presented. Accordingly to the in vitro data, compounds 1 and 2 were found to possess highly potent antiangiogenic activities in the cellular HLMEC sprouting assay and also slightly induced apoptosis in HDMECs whereas 3 was determined to be significantly less active. Hence, the pyrrole-2-one moiety was dissected from the corresponding maleimide protein kinase inhibitor as a suitable key pharmacophore.

  DOI：

  10.1021/jm8001185
• 作为产物：
  描述：

  N-(2-oxo-2-(1-((2-trimethylsilyl)ethoxymethyl)-1H-indol-3-yl)ethyl)-2-(3,4,5-trimethoxyphenyl)acetamide 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以66%的产率得到3-(3,4,5-trimethoxyphenyl)-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indol-3-yl)-1,5-dihydro-2H-pyrrole-2-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel 3-Aryl-4-(1H-indole-3yl)-1,5-dihydro-2H-pyrrole-2-ones as Vascular Endothelial Growth Factor Receptor (VEGF-R) Inhibitors

  摘要：

  In this study we report on the design, synthesis, and biological evaluation of pyrrole-2-one 2 to be a highly potent VEGF-R2/3 inhibitor with IC50 of 31/37 nM. The novel 3,4-diaryl-2H-pyrrole-2-ones were designed on the basis of the modeled binding mode of the corresponding 1H-pyrrole-2,5-dione (maleimide) VEGFR2/3 inhibitor I indicating two H-bond ligand-protein interactions in the ATP pocket for the amide 2 but not for the isomer 3. Flexible synthetic routes to 3,4-diaxyl-2H-pyrrole-2-ones and structure - activity relationships for the compounds in a panel of 24 therapeutically relevant protein kinases (IC50 values) are presented. Accordingly to the in vitro data, compounds 1 and 2 were found to possess highly potent antiangiogenic activities in the cellular HLMEC sprouting assay and also slightly induced apoptosis in HDMECs whereas 3 was determined to be significantly less active. Hence, the pyrrole-2-one moiety was dissected from the corresponding maleimide protein kinase inhibitor as a suitable key pharmacophore.

  DOI：

  10.1021/jm8001185

文献信息

• Design, Synthesis, and Biological Evaluation of Novel 3-Aryl-4-(1<i>H</i>-indole-3yl)-1,5-dihydro-2<i>H</i>-pyrrole-2-ones as Vascular Endothelial Growth Factor Receptor (VEGF-R) Inhibitors
  作者：Christian Peifer、Roland Selig、Katrin Kinkel、Dimitri Ott、Frank Totzke、Christoph Schächtele、Regina Heidenreich、Martin Röcken、Dieter Schollmeyer、Stefan Laufer

  DOI：10.1021/jm8001185

  日期：2008.7

  In this study we report on the design, synthesis, and biological evaluation of pyrrole-2-one 2 to be a highly potent VEGF-R2/3 inhibitor with IC50 of 31/37 nM. The novel 3,4-diaryl-2H-pyrrole-2-ones were designed on the basis of the modeled binding mode of the corresponding 1H-pyrrole-2,5-dione (maleimide) VEGFR2/3 inhibitor I indicating two H-bond ligand-protein interactions in the ATP pocket for the amide 2 but not for the isomer 3. Flexible synthetic routes to 3,4-diaxyl-2H-pyrrole-2-ones and structure - activity relationships for the compounds in a panel of 24 therapeutically relevant protein kinases (IC50 values) are presented. Accordingly to the in vitro data, compounds 1 and 2 were found to possess highly potent antiangiogenic activities in the cellular HLMEC sprouting assay and also slightly induced apoptosis in HDMECs whereas 3 was determined to be significantly less active. Hence, the pyrrole-2-one moiety was dissected from the corresponding maleimide protein kinase inhibitor as a suitable key pharmacophore.