2-(1H-indol-3-yl)-N-[2-(4-methoxyphenyl)-2-oxoethyl]acetamide | 1038914-93-0

• 英文名称: 2-(1H-indol-3-yl)-N-[2-(4-methoxyphenyl)-2-oxoethyl]acetamide
• CAS: 1038914-93-0
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: KQDDVMVPVIEJJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1H-indol-3-yl)-N-[2-(4-methoxyphenyl)-2-oxoethyl]acetamide 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以50%的产率得到3-(1H-indol-3-yl)-4-(4-methoxyphenyl)-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：

  4-甲氧基苯乙烯 在 盐酸 、 sodium azide 、 一氯化碘 作用下， 以 二氯甲烷 、 氘代甲醇-d 、 水 、 乙腈 为溶剂， 反应 6.0h， 生成 2-(1H-indol-3-yl)-N-[2-(4-methoxyphenyl)-2-oxoethyl]acetamide
  参考文献：
  名称：

  Rapid and Bifunctional Chemoselective Metabolome Analysis of Liver Disease Plasma Using the Reagent 4‐Nitrophenyl‐2H‐azirine

  摘要：

  Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts that has been associated with diverse metabolic carboxylic acids. Mass spectrometric techniques are the method of choice for their analysis. However, the broad investigation of this metabolite class remains challenging. Derivatization of carboxylic acids represents a strategy to overcome these limitations but available methods suffer from diverse analytical challenges. Herein, we have designed a novel strategy introducing 4‐nitrophenyl‐2H‐azirine as a new chemoselective moiety for the first time for carboxylic acid metabolites. This moiety was selected as it rapidly forms a stable amide bond and also generates a new ketone, which can be analyzed by our recently developed quant‐SCHEMA method specific for carbonyl metabolites. Optimization of this new method revealed a high reproducibility and robustness, which was utilized to validate 102 metabolic carboxylic acids using authentic synthetic standard conjugates in human plasma samples including nine metabolites that were newly detected. Using this sequential analysis of the carbonyl‐ and carboxylic acid‐metabolomes revealed alterations of the ketogenesis pathway, which demonstrates the vast benefit of our unique methodology. We anticipate that the developed azirine moiety with rapid functional group transformation will find broad application in diverse chemical biology research fields.

  DOI：

  10.1002/anie.202318579

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.