3-{[5-(3,4,5-trimethoxyphenyl)-1,3-oxazol-2-yl]methyl}-1H-indole | 1038914-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-{[5-(3,4,5-trimethoxyphenyl)-1,3-oxazol-2-yl]methyl}-1H-indole
• CAS: 1038914-72-5
• 化学式: C₂₁H₂₀N₂O₄
• 分子量: 364.401
• InChiKey: OWPSAXCNKNJXQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  69.51
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  3-吲哚乙酸 、 1-bromo-2-oxo-2-(3,4,5-trimethoxyphenyl)ethanaminium bromide 在 五氯化磷 、 吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 164.5h， 以22%的产率得到3-{[5-(3,4,5-trimethoxyphenyl)-1,3-oxazol-2-yl]methyl}-1H-indole
  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