3-(1’-methyl-1’H-indol-3’-yl)-4-(3”,4”,5”-trimethoxyphenyl)-1H-pyrrol-2(5H)-one | 1038914-92-9

• 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-(1’-methyl-1’H-indol-3’-yl)-4-(3”,4”,5”-trimethoxyphenyl)-1H-pyrrol-2(5H)-one
• 英文别名: 3-(N-methyl-1H-indol-3-yl)-4-(3,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrole-2-one；4-(1-methylindol-3-yl)-3-(3,4,5-trimethoxyphenyl)-1,2-dihydropyrrol-5-one
• CAS: 1038914-92-9
• 化学式: C₂₂H₂₂N₂O₄
• 分子量: 378.428
• InChiKey: DUPIINAVKMGMHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  61.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1’-methyl-1’H-indol-3’-yl)-4-(3”,4”,5”-trimethoxyphenyl)-1H-pyrrol-2(5H)-one 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以73%的产率得到2-(N-methyl-1H-indol-3-yl)-N-[2-(3,4,5-trimethoxyphenyl)-2-oxoethyl]acetamide
  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：

  1-甲基-3-吲哚乙酸 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 potassium tert-butylate 、 sodium carbonate 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 3-(1’-methyl-1’H-indol-3’-yl)-4-(3”,4”,5”-trimethoxyphenyl)-1H-pyrrol-2(5H)-one
  参考文献：
  名称：

  二芳基-3-吡咯啉-2-酮及其稠合类似物的合成及其抗增殖活性的评价

  摘要：

  制备包含具有不同甲氧基苯基和/或吲哚取代基的中心3-吡咯啉-2-酮核的类似物，并测试其在U-937细胞中的抗增殖活性。最有效的类似物是非刚性的（非稠合的），其位于4-位含有甲氧基芳基，并且位于3-位含有甲氧基芳基或吲哚基。取代基中所含的甲氧基的数目以及相对于内酰胺羰基的吲哚环的特定位置均对抗增殖活性具有显着影响。这项工作提供了一个框架，以更好地了解在二芳基杂环支架中诱导抗增殖活性的结构活性关系。

  DOI：

  10.1016/j.bmcl.2016.11.076

文献信息

• [DE] CYCLISCHE AMIDVERBINDUNGEN, VERFAHREN ZU DEREN HERSTELLUNG UND IHRE VERWENDUNG<br/>[EN] CYCLIC AMIDE COMPOUNDS, METHOD FOR THE PRODUCTION THEREOF AND THE USE THEREOF<br/>[FR] COMPOSÉS D'AMIDES CYCLIQUES, LEUR PROCÉDÉ DE PRODUCTION ET LEUR UTILISATION
  申请人：UNIV EBERHARD KARLS

  公开号：WO2009010542A1

  公开（公告）日：2009-01-22

  Die Erfindung betrifft cyclische Amidverbindungen der allgemeinen Formel (I), worin R1 und R2 in Anspruch 1 definiert sind. Die Erfindung betrifft ferner das Verfahren zur Herstellung der Verbindungen der Formel (I), pharmazeutische Mittel enthaltend wenigstens eine dieser Verbindungen sowie deren Verwendung zur Angiogenesehemmung und zur Prävention und/oder Therapie von mit Angiogenese assoziierten Krankheiten, insbesondere Krebserkrankungen.
• Synthesis and evaluation of the anti-proliferative activity of diaryl-3-pyrrolin-2-ones and fused analogs
  作者：Patricia Mowery、Fernando Banales Mejia、Courtney L. Franceschi、Maeve H. Kean、Deborah O. Kwansare、Megan M. Lafferty、Namita D. Neerukonda、Carly E. Rolph、Nathanyal J. Truax、Erin T. Pelkey

  DOI：10.1016/j.bmcl.2016.11.076

  日期：2017.1

  Analogs containing a central 3-pyrrolin-2-one core with different methoxyphenyl and/or indole substituents were prepared and tested for anti-proliferative activity in U-937 cells. The most efficacious analogs were non-rigid, (non-fused) contained methoxyaryl groups located at the 4-position, and contained either methoxyaryl or indole groups located at the 3-position. Both the number of methoxy groups

  制备包含具有不同甲氧基苯基和/或吲哚取代基的中心3-吡咯啉-2-酮核的类似物，并测试其在U-937细胞中的抗增殖活性。最有效的类似物是非刚性的（非稠合的），其位于4-位含有甲氧基芳基，并且位于3-位含有甲氧基芳基或吲哚基。取代基中所含的甲氧基的数目以及相对于内酰胺羰基的吲哚环的特定位置均对抗增殖活性具有显着影响。这项工作提供了一个框架，以更好地了解在二芳基杂环支架中诱导抗增殖活性的结构活性关系。
• 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.