(E)-3-(2-hydroxy-4-methoxybenzylidene)indolin-2-one | 1148118-94-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-3-(2-hydroxy-4-methoxybenzylidene)indolin-2-one
• 英文别名: (3E)-3-[(2-hydroxy-4-methoxyphenyl)methylidene]-1H-indol-2-one
• CAS: 1148118-94-8
• 化学式: C₁₆H₁₃NO₃
• 分子量: 267.284
• InChiKey: NMJZKVHHPSTXPH-MDWZMJQESA-N

物化性质

• 熔点：
  149-152 °C
• 沸点：
  548.3±50.0 °C(predicted)
• 密度：
  1.327±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 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：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(2-hydroxy-4-methoxybenzylidene)indolin-2-one 、 丁烯-2-醛 在 (2S)-2-[二苯基[(三甲基硅酯)氧基]甲基]-吡咯烷 、 邻三氟甲基苯甲酸 作用下， 以 氯仿 为溶剂， 反应 36.0h， 以99%的产率得到
  参考文献：
  名称：

  通过不对称有机催化四级联反应 有效构建生物学上重要的功能化多环螺旋稠合碳环氧吲哚†

  摘要：

  通过（E）的不对称有机催化四重多米诺反应，开发了高功能化多环螺环碳杂环吲哚的有效结构。）-3-（2-羟基亚苄基）氧吲哚衍生物和两个分子的亚胺-亚胺-亚胺-亚胺四重催化下的α，β-不饱和醛分子。获得具有螺四元中心和五个连续立体中心的复杂级联产物，具有中等至高产率（高达90％），非对映选择性好（高达8：1）和出色的ee值（高达99％ee）。产物的结构和绝对构型通过NMR光谱和单晶X射线分析证实。另外，生物学研究表明这些化合物在微摩尔范围内具有中等的抗肿瘤活性。

  DOI：

  10.1039/c6ra24910h
• 作为产物：
  描述：

  靛红 在 哌啶 、 一水合肼 作用下， 以 乙醇 为溶剂， 生成 (E)-3-(2-hydroxy-4-methoxybenzylidene)indolin-2-one
  参考文献：
  名称：

  Discovery of novel polycyclic spiro-fused carbocyclicoxindole-based anticancer agents

  摘要：

  A series of novel polycyclic spiro-fused carbocyclicoxindoles were synthesized and investigated for their in vitro antiproliferative activities against nine human cancer cell lines. Five compounds (10i, 101, 10n, 10p, and 10r) demonstrated anticancer activities against A2780s cells with IC50 values of less than 30 mu M. In particular, compound 10i showed anticancer activities against seven cancer cell lines and stronger activities than cisplatin in A2780s, A2780T, L126, and HCT116 cells. Further studies illustrated that compound 101 arrested cell cycle in G1 phase and induced apoptosis of HCT116 cells. This compound also effectively increased the protein levels of cleaved caspase-3, p53, and MDM2. Molecular docking results revealed that compound 101 could bind well to the p53-binding site on MDM2, indicating that it might work by blocking the MDM2-p53 interactions. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.12.021

文献信息

• Efficient construction of biologically important functionalized polycyclic spiro-fused carbocyclicoxindoles via an asymmetric organocatalytic quadruple-cascade reaction
  作者：Wen Ren、Xiao-Yan Wang、Jing-Jing Li、Mao Tian、Jie Liu、Liang Ouyang、Jin-Hui Wang

  DOI：10.1039/c6ra24910h

  日期：——

  efficient construction of highly functionalized polycyclic spiro-fused carbocyclicoxindoles has been developed via an asymmetric organocatalytic quadruple domino reaction of (E)-3-(2-hydroxybenzylidene)oxindole derivatives and two molecules of α,β-unsaturated aldehyde under quadruple iminium–enamine–iminium–enamine catalysis. The complex cascade products bearing a spiro quaternary center and five contiguous

  通过（E）的不对称有机催化四重多米诺反应，开发了高功能化多环螺环碳杂环吲哚的有效结构。）-3-（2-羟基亚苄基）氧吲哚衍生物和两个分子的亚胺-亚胺-亚胺-亚胺四重催化下的α，β-不饱和醛分子。获得具有螺四元中心和五个连续立体中心的复杂级联产物，具有中等至高产率（高达90％），非对映选择性好（高达8：1）和出色的ee值（高达99％ee）。产物的结构和绝对构型通过NMR光谱和单晶X射线分析证实。另外，生物学研究表明这些化合物在微摩尔范围内具有中等的抗肿瘤活性。
• Functionalized 3-benzylidene-indolin-2-ones: Inducers of NAD(P)H-quinone oxidoreductase 1 (NQO1) with antiproliferative activity
  作者：Wei Zhang、Mei-Lin Go

  DOI：10.1016/j.bmc.2008.12.052

  日期：2009.3

  Functionalized benzylidene-indolin-2-ones are widely associated with antiproliferative activity. The scaffold is not normally associated with chemoprevention in spite of the presence of a nitrogen-linked Michael acceptor moiety that may predispose members to induction of NQO1, a widely used biomarker of chemopreventive potential. To investigate this possibility, we have synthesized and evaluated a series of functionalized 3-benzylidene-indolin-2-ones for induction of NQO1 in murine Hepa1c1c7 cells as well as antiproliferative activity against two human cancer cell lines (MCF-7, HCT116). The benzylideneindolinones were found to be good inducers of NQO1 activity, with 85% of test compounds able to increase basal NQO1 activity by more than twofold at concentrations of <= 10 mu M. By contrast, fewer compounds (11%) tested at the same concentration were able to reduce cell viability by more than 50%. Structure activity relationships showed that the nitrogen linked Michael acceptor moiety was an essential requirement for both activities. This common feature notwithstanding, substitution of the 3-benzylidene-indolin-2-one core structure affected NQO1 induction and antiproliferative activities in dissimilar ways, underscoring different structural requirements for these two activities. Nonetheless, promising compounds ( 10, 42, 45-48) were identified that combine selective induction of NQO1 with potent antiproliferative activity. A potential advantage of such agents would be the ability to provide added protection to normal cells by the up-regulation of NQO1 and other phase II enzymes while simultaneously targeting neoplastic cells. (C) 2008 Elsevier Ltd. All rights reserved.
• Discovery of novel polycyclic spiro-fused carbocyclicoxindole-based anticancer agents
  作者：Lidan Zhang、Wen Ren、Xiaoyan Wang、Jiaying Zhang、Jie Liu、Lifeng Zhao、Xia Zhang

  DOI：10.1016/j.ejmech.2016.12.021

  日期：2017.1

  A series of novel polycyclic spiro-fused carbocyclicoxindoles were synthesized and investigated for their in vitro antiproliferative activities against nine human cancer cell lines. Five compounds (10i, 101, 10n, 10p, and 10r) demonstrated anticancer activities against A2780s cells with IC50 values of less than 30 mu M. In particular, compound 10i showed anticancer activities against seven cancer cell lines and stronger activities than cisplatin in A2780s, A2780T, L126, and HCT116 cells. Further studies illustrated that compound 101 arrested cell cycle in G1 phase and induced apoptosis of HCT116 cells. This compound also effectively increased the protein levels of cleaved caspase-3, p53, and MDM2. Molecular docking results revealed that compound 101 could bind well to the p53-binding site on MDM2, indicating that it might work by blocking the MDM2-p53 interactions. (C) 2016 Elsevier Masson SAS. All rights reserved.