5-(4-fluorobenzyl)-2,3,4-trimethoxybenzaldehyde | 1377834-00-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-fluorobenzyl)-2,3,4-trimethoxybenzaldehyde
• CAS: 1377834-00-8
• 化学式: C₁₇H₁₇FO₄
• 分子量: 304.318
• InChiKey: AFFXNPGPMJNIAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-(4-fluorobenzyl)-2,3,4-trimethoxybenzaldehyde 在 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 氯仿 、 二甲基亚砜 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Synthesis of new mixed phenol/heterocyclic derivatives and studies of their activity as inhibitors of Bax/Bcl-xL interaction

  摘要：

  We describe here the synthesis of a series of new molecules containing phenol and heteroaromatic moieties, compounds, which have been evaluated for their ability to inhibit Bax/Bcl-xL interactions in BRET assays. Among them, a triazole derivative 13, exhibit a very promising activity, being more potent than the reference compounds acylpyrogallol 1 and ABT 737. These preliminary results demonstrate that derivatives of this family can be attractive to develop new molecules with potent anticancer activity. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.11.060

文献信息

• Preliminary Studies on the Activity of Mixed Polyphenol-Heterocyclic Systems Against B16-F10 Melanoma Cancer Cells
  作者：Duc Duy Vo、Isabelle Rouaud、Francoise Le Devehat、Fabien Gautier、Sophie Barillé-Nion、Philippe Juin、Nicolas Levoin、Joël Boustie、René Grée

  DOI：10.2174/1573406412666160129104603

  日期：2016.6.23

  The Bcl-2 family includes 26 proteins involved in apoptosis. Cancer cells can develop the ability to avoid apoptosis through the upregulation and/or down regulation of such proteins Bax, Bcl-xL or Mcl-1, especially during chemoresistance progress. These proteins engaged in a network of dynamic interactions that control apoptosis triggering have become attractive therapeutic targets in cancers including melanoma. Among them, the Bax/Bcl-xL interaction appears critical in maintaining mitochondria integrity. Therefore a series of mixed polyphenol-heterocyclic molecules, were rationally designed by molecular docking as Bax/Bcl-xL inhibitors. It has been screened against B16-F10 melanoma cancer cells for a preliminary investigation of their cytotoxicity. All these compounds exhibited a significant cytotoxicity against these cancer cells, in the 0.3-6 M range. A pyrazole-type molecule, which had a submicromolar IC50 value with an excellent selectivity index (14), is the most promising derivative for further development.

  Bcl-2 家族包括 26 种参与细胞凋亡的蛋白质。癌细胞可以通过上调和/或下调 Bax、Bcl-xL 或 Mcl-1 等蛋白来避免凋亡，尤其是在化疗抗药性进展期间。这些参与控制细胞凋亡触发的动态相互作用网络的蛋白质已成为包括黑色素瘤在内的癌症的诱人治疗靶点。其中，Bax/Bcl-xL 的相互作用似乎对维持线粒体的完整性至关重要。因此，我们通过分子对接合理地设计了一系列混合多酚杂环分子，作为 Bax/Bcl-xL 抑制剂。针对 B16-F10 黑色素瘤癌细胞进行了筛选，对其细胞毒性进行了初步研究。所有这些化合物在 0.3-6 M 的范围内对这些癌细胞都有明显的细胞毒性。一种吡唑类分子的 IC50 值为亚摩尔级，具有极佳的选择性指数 (14)，是最有希望进一步开发的衍生物。
• A combination of in silico and SAR studies to identify binding hot spots of Bcl-xL inhibitors
  作者：Nicolas Levoin、Duc Duy Vo、Fabien Gautier、Sophie Barillé-Nion、Philippe Juin、Olivier Tasseau、René Grée

  DOI：10.1016/j.bmc.2015.02.060

  日期：2015.4

  Inhibition of Bcl-2 family protein–protein interactions (PPI) is a very promising direction in cancer chemotherapy. Hence over the last decade, many medicinal chemistry studies endeavoured to discover drug candidates, and a wealth of chemical scaffolds with striking chemical diversity was reported as Bcl-xL inhibitors. This raises the question of whether all these molecules could occupy a unique binding site

  抑制Bcl-2家族蛋白-蛋白相互作用（PPI）是癌症化疗中非常有希望的方向。因此，在过去的十年中，许多药物化学研究都致力于发现候选药物，据报道，许多具有惊人化学多样性的化学支架是Bcl-xL抑制剂。这就提出了一个问题，即所有这些分子是否都可以占据一个独特的结合位点，或者占据蛋白质表面的离散口袋。 为了测试小型且化学上不同的Bcl-xL抑制剂是否可能结合单个口袋，并确定哪个口袋，我们使用了一系列计算和建模方法。我们首先检查了我们构建的Bcl-xL抑制剂的大型数据集是否确实可以适合通用药效团。然后，我们通过比较晶体结构以及虚拟片段筛选，确定了相互作用的可能结合热点。最后，合成了小多酚衍生物的新类似物，以精确探测对接实验表明的氢键。这些产物的Bcl-xL抑制效力证实了预测的结合模式。 X射线结构探索，分子模型研究和药物化学的这种结合支持所有这些小的Bcl-xL抑制剂占据相同的相互作用热点。该结合位点的鉴定应有助于设计和优化小的PPI
• Design, synthesis and biological evaluation of new inhibitors of Bax/Bcl-xL interaction in cancer cells
  作者：Duc Duy Vo、Fabien Gautier、Sophie Barillé-Nion、Philippe Juin、Nicolas Levoin、René Grée

  DOI：10.1016/j.bmcl.2014.02.035

  日期：2014.4

  We describe the synthesis of a series of new molecules containing phenol and triazoles moieties, compounds which have been evaluated for their ability to inhibit Bax/Bcl-xL interactions in cancer cells, by using BRET assays, and to induce cell death. Several derivatives exhibit a very promising activity, being more potent than the reference compounds acylpyrogallol and ABT-737. These preliminary results

  我们描述了一系列含有苯酚和三唑部分的新分子的合成，这些化合物已通过使用 BRET 测定来评估其抑制癌细胞中 Bax/Bcl-xL 相互作用的能力以及诱导细胞死亡的能力。几种衍生物表现出非常有前途的活性，比参考化合物酰基连苯三酚和 ABT-737 更有效。这些初步结果表明，该家族的衍生物对于开发具有有效抗癌活性的新分子具有吸引力。
• Structure–activity relationship of selected polyphenol derivatives as inhibitors of Bax/Bcl-xL interaction
  作者：Duc Duy Vo、Fabien Gautier、Philippe Juin、René Grée

  DOI：10.1016/j.ejmech.2012.02.036

  日期：2012.5

  This paper describes the synthesis of nine selected diaryl/heteroaryl-containing phenol and polyphenol derivatives which have been evaluated against Bax/Bcl-xL interaction in comparison with ABT-737. Using a BRET assay, six of these derivatives exhibit activity comparable to ABT-737 to disrupt Bax/Bcl-xL interaction. These preliminary results demonstrate that such polyphenol-derived molecules are attractive compounds regarding anticancer activity and that the phenol at position 3 is important regarding disruption of Bax/Bcl-xL interaction. (C) 2012 Elsevier Masson SAS. All rights reserved.