3-(4‘-methoxybenzylidene)-5-nitroindolin-2-one | 1206720-20-8

• 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-(4‘-methoxybenzylidene)-5-nitroindolin-2-one
• 英文别名: 3-[(4-methoxyphenyl)methylidene]-5-nitro-1H-indol-2-one
• CAS: 1206720-20-8
• 化学式: C₁₆H₁₂N₂O₄
• 分子量: 296.282
• InChiKey: PCQKCZRQZTVYQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4‘-methoxybenzylidene)-5-nitroindolin-2-one 在 盐酸 、 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 生成 (E)-5-amino-3-(4-methoxybenzylidene)indolin-2-one 、 (Z)-5-amino-3-(4-methoxybenzylidene)indolin-2-one
  参考文献：
  名称：

  Synthesis, structure–activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors

  摘要：

  The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped re. ne SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.011
• 作为产物：
  描述：

  2-吲哚酮 在 哌啶 、 硫酸 、 potassium nitrate 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 3-(4‘-methoxybenzylidene)-5-nitroindolin-2-one
  参考文献：
  名称：

  一些 E/Z 3-(亚苄基)-2-氧代-二氢吲哚衍生物的反转动力学及其计算机 CDK2 对接研究

  摘要：

  实现了一些具有 3-(亚苄基)吲哚啉-2-酮支架的 CDK2 抑制剂的基于结构的设计作为潜在的抗癌药物。获得E / Z混合物形式的目标化合物，并将其拆分为相应的E-和Z-非对映体。使用 MOE 2019.01 软件进行的计算机模拟研究表明，与E -one 相比， Z-非对映体与目标酶的对接效果更好。对室温下DMSO-d 6中E / Z非对映异构体的转化进行了时间依赖性动力学异构化研究，发现其服从一级动力学反应。此外，通过图形分析方法确定了动力学相互转化速率级，并计算了该动力学过程的速率常数和半衰期。为了预测非对映异构体的稳定性，异构化反应速率和一些具有显着p值的 QM 参数之间生成了良好的多元回归方程。

  DOI：

  10.1039/d0ra10672k

文献信息

• New cell cycle checkpoint pathways regulators with 2-Oxo-indoline scaffold as potential anticancer agents: Design, synthesis, biological activities and in silico studies
  作者：Hend A.A. Abd El-wahab、Hany S. Mansour、Ahmed M. Ali、Raafat El-Awady、Tarek Aboul-Fadl

  DOI：10.1016/j.bioorg.2022.105622

  日期：2022.3

  Compounds 5a, 5b, 5e1, 5m, 6f and 6j were tested for the effect on the expression on CDK2, p53, caspase-3 and caspase-9 proteins, and revealed variable activities compared to the positive controls Sunitinib and Staurosporine. These molecules seem to have multiple cellular targets as they induced expression of p53 and caspases while inhibited that of CDK2. Apoptotic effect of compound 6j was further investigated

  3-Arylidene-2-oxo-indoline 衍生物是 2-oxo-indolines 中广泛的临床、医学和生物学重要化合物的核心。许多 3-arylidene-2-oxo-indolines 已被批准用于临床应用。因此，目前的工作描述了 3-亚芳基-2-羟吲哚衍生物的结构设计，通过将它们的结构对接在 CDK2 的活性位点作为主要酶检查点之一。基于对接研究，一系列 3-arylidene-2-oxindole 衍生物，5(an)和6(ax)，在 2-oxindole 的 1 和 5 位以及芳基部分的 3 和 4 位具有可变取代基被合成了。这些分子存在于E或Z羟吲哚核3位环外双键的非对映异构体。它们的结构通过光谱和元素分析方法得到证实，非对映异构体的E/Z构型通过二维 NOE分析得到证实。这些分子的体外细胞毒性针对四种癌细胞系进行了测试，即乳腺癌细胞系（MCF7）、肝癌细胞系（Hep
• Synthesis, structure–activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors
  作者：Luca Mologni、Roberta Rostagno、Stefania Brussolo、Phillip P. Knowles、Svend Kjaer、Judith Murray-Rust、Enrico Rosso、Alfonso Zambon、Leonardo Scapozza、Neil Q. McDonald、Vittorio Lucchini、Carlo Gambacorti-Passerini

  DOI：10.1016/j.bmc.2010.01.011

  日期：2010.2

  The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped re. ne SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers. (C) 2010 Elsevier Ltd. All rights reserved.
• Inversion kinetics of some <i>E</i>/<i>Z</i> 3-(benzylidene)-2-oxo-indoline derivatives and their <i>in silico</i> CDK2 docking studies
  作者：Hany S. Mansour、Hend A. A. Abd El-wahab、Ahmed M. Ali、Tarek Aboul-Fadl

  DOI：10.1039/d0ra10672k

  日期：——

  reactions. Furthermore, a determination of the kinetic inter-conversion rate order by graphical analysis method and calculation of the rate constant and half-life of this kinetic process were carried out. For the prediction of the stability of the diastereomer(s), a good multiple regression equation was generated between the reaction rates of isomerization and some QM parameters with significant p value.

  实现了一些具有 3-(亚苄基)吲哚啉-2-酮支架的 CDK2 抑制剂的基于结构的设计作为潜在的抗癌药物。获得E / Z混合物形式的目标化合物，并将其拆分为相应的E-和Z-非对映体。使用 MOE 2019.01 软件进行的计算机模拟研究表明，与E -one 相比， Z-非对映体与目标酶的对接效果更好。对室温下DMSO-d 6中E / Z非对映异构体的转化进行了时间依赖性动力学异构化研究，发现其服从一级动力学反应。此外，通过图形分析方法确定了动力学相互转化速率级，并计算了该动力学过程的速率常数和半衰期。为了预测非对映异构体的稳定性，异构化反应速率和一些具有显着p值的 QM 参数之间生成了良好的多元回归方程。