1,3-DiMethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene | 173306-05-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1,3-DiMethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene
• 英文别名: 1,3-dimethoxy-5-[2-(4-nitrophenyl)ethenyl]benzene
• CAS: 173306-05-3
• 化学式: C₁₆H₁₅NO₄
• 分子量: 285.299
• InChiKey: ZOKYIFYCPTXDCW-UHFFFAOYSA-N

物化性质

• 沸点：
  425.3±35.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-DiMethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene 在 碘 作用下， 以 氯仿 为溶剂， 反应 12.0h， 以96%的产率得到(E)-1,3-二甲氧基-5-(4-硝基苯乙烯基)苯
  参考文献：
  名称：

  The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues

  摘要：

  A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45 +/- 0.82 mu M. The antitumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.022
• 作为产物：
  描述：

  对硝基溴化苄 在 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 1,3-DiMethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene
  参考文献：
  名称：

  发现用于治疗实体癌的 STAT3 和组蛋白脱乙酰酶 (HDAC) 双通路抑制剂

  摘要：

  如今，由于肿瘤发生背后的复杂机制，通过药物组合同时抑制多个靶点是一种重要的抗癌策略。最近的研究表明，组蛋白去乙酰化酶 (HDAC) 的抑制将导致乳腺癌中臭名昭著的癌症相关药物靶标、信号转导和转录激活因子 3 (STAT3) 的补偿激活，这可能会限制抗-HDAC抑制剂在实体瘤中的增殖作用。通过将HDAC抑制剂SAHA（伏立诺他）的药效团并入STAT3抑制剂紫檀芪中，合成了一系列具有双靶点抑制活性的有效紫檀芪异羟肟酸衍生物。一种极好的异羟肟酸酯衍生物，化合物14，抑制 STAT3（K D = 33 nM) 和 HDAC (IC 50 = 23.15 nM)在体外具有强大的效力。化合物14在体内和体外也显示出有效的抗增殖能力。我们的研究为进一步探索提供了第一个 STAT3 和 HDAC 双靶点抑制剂。

  DOI：

  10.1021/acs.jmedchem.1c00136

文献信息

• Discovery of Novel Pterostilbene-Based Derivatives as Potent and Orally Active NLRP3 Inflammasome Inhibitors with Inflammatory Activity for Colitis
  作者：Liu Zeng Chen、Xing Xing Zhang、Ming Ming Liu、Jing Wu、Duo Ma、Liang Zhuo Diao、Qingshan Li、Yan Shuang Huang、Rui Zhang、Ban Feng Ruan、Xin Hua Liu

  DOI：10.1021/acs.jmedchem.1c01007

  日期：2021.9.23

  Studies have shown that the abnormal activation of the NLRP3 inflammasome is involved in a variety of inflammatory-based diseases. In this study, a high content screening model targeting the activation of inflammasome was first established and pterostilbene was discovered as the active scaffold. Based on this finding, total of 50 pterostilbene derivatives were then designed and synthesized. Among them

  研究表明NLRP3炎症小体的异常激活与多种炎症性疾病有关。本研究首次建立了针对炎症小体激活的高内涵筛选模型，并发现紫檀芪作为活性支架。基于这一发现，设计并合成了总共50种紫檀芪衍生物。其中，化合物47被发现是抑制细胞焦亡最好的一种[抑制率(IR) = 73.09% at 10 μM]，表现出低毒高效[针对白细胞介素-1β(IL-1β)：半最大抑制浓度(IC 50 ) = 0.56 μM]。进一步的研究表明，化合物47通过靶向NLRP3影响NLRP3炎症小体的组装。体内生物活性表明，该化合物可显着减轻右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎。总的来说，我们的研究提供了一种直接靶向NLRP3蛋白的新型先导化合物，值得进一步研究和结构优化。
• Convenient One-Step Synthesis of Benzo[<i>c</i>]phenanthridines by Three-Component Reactions of Isochromenylium Tetrafluoroborates and Stilbenes in Acetonitrile
  作者：Gang-Gang Chen、Jun-Qiang Wei、Xiaoliang Yang、Zhu-Jun Yao

  DOI：10.1021/acs.orglett.6b00010

  日期：2016.4.1

  A new type of three-component reaction of air-stable isochromenylium tetrafluoroborates with electron-rich stilbenes in acetonitrile has been developed under catalyst-free conditions in this work. This cascade multibond-formation reaction is initiated by an intermolecular oxa [4 + 2]-cycloaddition, relayed with a nucleophilic addition of acetonitrile, and terminated by an intramolecular Friedel–Crafts

  在这项工作中，在无催化剂条件下，开发了一种新型的空气稳定的四氟硼酸异铬腈与乙腈中富含电子的对苯二甲酸酯的三组分反应。这种级联的多键形成反应由分子间的氧杂[4 + 2]-环加成反应引发，再与乙腈进行亲核加成反应，再由分子内的Friedel-Crafts反应终止，一步即可得到相应的苯并[ c ]菲啶类似物。
• Al-containing mesoporous carbon as effective catalysts for the chemoselective reduction of carbon–carbon double bonds in nitrostilbene derivatives
  作者：Liuchang Wang、Yanjun Zheng、Xiquan Zhang、Hongmei Gu、Jiang Li、Wei Wang、Baolin Li

  DOI：10.1016/j.apcata.2013.01.040

  日期：2013.4

  reduction of carbon–carbon double bond in 4-nitrostilbene analogs bearing nitro group with hydrazine hydrate. The results indicated that the reduction reaction was able to be achieved successfully between carbon–carbon double bond and nitro group. The efficient method has been developed for the reduction of CC double bonds with diimide, catalytically generated in situ from hydrazine hydrate by the synthesized

  合成了一系列含Al，Mn，Cu和Fe的金属介孔碳催化剂，用于催化水合肼选择性还原带有硝基的4-硝基苯乙烯类似物中的碳-碳双键。结果表明，碳-碳双键与硝基之间能够成功地完成还原反应。已经开发出减少碳含量的有效方法C与二酰亚胺的双键由合成的催化剂由水合肼原位催化生成。0.15Al–MC1作为非均相催化剂在所有合成催化剂中均表现出最高的催化活性和化学选择性。在0.15Al-MC1存在下，在70°C的乙醇中，4-硝基二苯乙烯衍生物中碳-碳双键的还原率高达99％，化学选择性> 99％。另一方面，在惰性气氛下用水合肼，活性炭和FeCl 3 ·6H 2 O也容易实现4-亚硝基苯甲酸酯中硝基的高选择性还原。
• Novel resveratrol derivatives have diverse effects on the survival, proliferation and senescence of primary human fibroblasts
  作者：Vishal C. Birar、Angela N. Sheerin、Elizabeth L. Ostler、Richard G. A. Faragher

  DOI：10.1007/s10522-020-09896-6

  日期：2020.12

  Resveratrol alters the cytokinetics of mammalian cell populations in a dose dependent manner. Concentrations above 25-50 mu M typically trigger growth arrest, senescence and/or apoptosis in multiple different cell types. In contrast, concentrations below 10 mu M enhance the growth of log phase cell cultures and can rescue senescence in multiple strains of human fibroblasts. To better understand the structural features that regulate these effects, a panel of 24 structurally-related resveralogues were synthesised and evaluated for their capacity to activate SIRT1, as determined by an ex-vivo SIRT1 assay, their toxicity, as measured by lactate dehydrogenase release, and their effects on replicative senescence in MRC5 human fibroblasts as measured by their effects on Ki67 immunoreactivity and senescence-associated beta galactosidase activity. Minor modifications to the parent stilbene, resveratrol, significantly alter the biological activities of the molecules. Replacement of the 3,5-dihydroxy substituents with 3,5-dimethoxy groups significantly enhances SIRT1 activity, and reduces toxicity. Minimising other strong conjugative effects also reduces toxicity, but negatively impacts SIRT1 activation. At 100 mu M many of the compounds, including resveratrol, induce senescence in primary MRC5 cells in culture. Modifications that reduce or remove this effect match those that reduce toxicity leading to a correlation between reduction in labelling index and increase in LDH release. At 10 mu M, the majority of our compounds significantly enhance the growth fraction of log phase cultures of MRC5 cells, consistent with the rescue of a subpopulation of cells within the culture from senescence. SIRT1 activation is not required for rescue to occur but enhances the size of the effect.
• The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues
  作者：Huachen Liu、Aijun Dong、Chunmei Gao、Chunyan Tan、Hongxia Liu、Xuyu Zu、Yuyang Jiang

  DOI：10.1016/j.bmc.2008.10.022

  日期：2008.12

  A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45 +/- 0.82 mu M. The antitumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway. (c) 2008 Elsevier Ltd. All rights reserved.