(Z)-2-(4-fluorobenzylidene)-6-hydroxybenzofuran-3(2H)-one | 139311-84-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 橙酮类黄酮
• 英文名称: (Z)-2-(4-fluorobenzylidene)-6-hydroxybenzofuran-3(2H)-one
• 英文别名: (2Z)-2-(4-fluorobenzylidene)-6-hydroxy-1-benzofuran-3(2H)-one；(2Z)-2-[(4-fluorophenyl)methylidene]-6-hydroxy-1-benzofuran-3-one
• CAS: 139311-84-5
• 化学式: C₁₅H₉FO₃
• mdl: MFCD04065085
• 分子量: 256.233
• InChiKey: LRUJRAQGJJEHMX-AUWJEWJLSA-N

物化性质

• 沸点：
  466.6±45.0 °C(Predicted)
• 密度：
  1.451±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  (Z)-2-(4-fluorobenzylidene)-6-hydroxybenzofuran-3(2H)-one 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 乙酸乙酯 、 丙酮 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 2-(4-Fluoro-benzyl)-6-methoxy-benzofuran-3-one
  参考文献：
  名称：

  Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis

  摘要：

  A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized. The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed by dehydration of the resulting carbinols. The benzofurans are ligands for antiestrogen-binding sites (AEBS) and display no significant interaction with the estrogen receptor (ER). All bind to AEBS with equivalent or greater affinity than tamoxifen. These compounds decrease [H-3]thymidine incorporation in AEBS-containing EL4 lymphoid cells and MCF7 breast cancer cells in a concentration-dependent manner between 10(-8) and 10(-6) M and are generally more inhibitory than tamoxifen. In contrast, they have no effect on [H-3]thymidine incorporation by an AEBS-deficient variant of the MCF7 cell line, RTx6. The present findings of (1) selective and high affinity binding of the benzofurans to AEBS, (2) their concentration-dependent inhibition of [H-3]thymidine incorporation in AEBS-containing cells, and (3) their lack of antiproliferative effect in an AEBS-deficient cell line suggest a functional role for AEBS in mediating the antigrowth effect of these compounds. Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER. This effect could be obtained after 5 h of treatment and preceded significant loss of cell viability. This is the first demonstration that selective ligands of AEBS (other than the known nonsteroidal antiestrogens) interfere with cholesterol biosynthesis-an action that may contribute to their antigrowth effect.

  DOI：

  10.1021/jm00086a002
• 作为产物：
  描述：

  间苯二酚 在 盐酸 、 sodium acetate 、 potassium hydroxide 、 zinc(II) chloride 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 反应 1.25h， 生成 (Z)-2-(4-fluorobenzylidene)-6-hydroxybenzofuran-3(2H)-one
  参考文献：
  名称：

  Discovery of aurones bearing two amine functionalities as SHIP2 inhibitors with insulin-sensitizing effect in rat myotubes

  摘要：

  带有两个胺官能团的醛酮 12a 是一种微摩尔 SHIP2 抑制剂，具有增强大鼠肌管葡萄糖摄取的特性。12a 在 Caco-2 细胞单层中表现出良好的渗透性，这表明它具有作为口服胰岛素增敏剂的潜力。

  DOI：

  10.1039/d3md00360d

文献信息

• Design, synthesis, and biological evaluation of a novel dual peroxisome proliferator-activated receptor alpha/delta agonist for the treatment of diabetic kidney disease through anti-inflammatory mechanisms
  作者：Kai Liu、Xing Zhao、Xue Qi、Dong-Liang Hou、Hao-Bin Li、Yu-Hao Gu、Qing-Long Xu

  DOI：10.1016/j.ejmech.2021.113388

  日期：2021.6

  a dual PPAR-α/δ agonist, and the selectivity against PPAR-γ is still to be improved. Sulfuretin has been shown to suppress the expression of PPAR-γ and improve the pathogenesis of diabetic complications. In this study, by hybridizing the carboxylic acid of GFT505 and the parent nucleus of sulfuretin, we pioneeringly designed and synthetized a series of novel dual PPAR-α/δ agonists, expecting to provide

  糖尿病肾病 (DKD) 是几乎所有病因类型糖尿病 (DM) 最后阶段的主要特征。迄今为止，很少有安全有效的药物可用于治疗。过氧化物酶体增殖物激活受体 (PPARs) 由三个成员组成：PPAR-α、PPAR-δ 和 PPAR-γ，通过血糖控制和脂质代谢在 DKD 中发挥保护作用，而 PPAR-γ 的全身激活会导致严重的副作用- 在临床试验中的作用。GFT505是双PPAR-α/δ激动剂，对PPAR-γ的选择性仍有待提高。Sulfuretin 已被证明可抑制 PPAR-γ 的表达并改善糖尿病并发症的发病机制。在本研究中，通过杂化GFT505的羧酸和硫磺素的母核，我们开创性地设计合成了一系列新型双 PPAR-α/δ 激动剂，期望为 PPARs 提供更好的收益/风险比。在所有合成的化合物中，化合物12被鉴定为对 PPAR-α/δ 具有高活性和对 PPAR-γ 的选择性高于GFT505（EC 50 :
• The first synthesis of peracetyl glycosyl aurone derivatives and aurone glucosides
  作者：Arjun Kafle、Shrijana Bhattarai、Scott T. Handy

  DOI：10.1016/j.tet.2020.131528

  日期：2020.10

  therapeutic importance, also exist in variously glycosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O-glycosylation was achieved by reacting 6-hydroxy aurones with 2, 3, 4, 6-tetra-O-acetyl-α-D

  证明具有重要治疗意义的类黄酮类金盏花也以各种糖基化形式存在。尽管已从植物来源中分离出大量糖基化的金酮衍生物，但尚未报道合成方法。从这种差距中得到启发，在这里我们报告了合成金黄色素的全乙酰化糖基衍生物的首次合成。直接的O-糖基化是通过使6-羟基金氧烷与2、3、4、6-四-O-乙酰基-α反应而实现的-D吡喃葡萄糖基溴化物在相转移催化剂四丁基溴化铵（TBAB）的存在下。以60-92％的产率成功合成金酮糖苷（33个实例）将有益于糖基化金酮组合库的合成，以用于生物学研究和与非糖基化金酮的比较。
• Synthesis and Activity of Aurone and Indanone Derivatives
  作者：Chao Niu、Haji Akber Aisa、Heng Wu、Haiqing Zhao、Tong Lu、Baoxing Xie

  DOI：10.2174/1573406419666230203105246

  日期：2023.2.3

  Gram-positive bacteria. The introduction of electron-withdrawing groups or hydroxyl is beneficial to the activity. It was exciting that the 3-phenylallylbenzofuranone and 3-allylindanone skeletons with antimicrobial activity were first reported in this study. Compounds A5 and E7 were selected for molecular docking studies with targets MetRS (PBD: 7WPI) and PBP (PDB: 6C3K) to determine the binding interactions

  简介：基于生物活性基团剪接、经典生物电子等排和烯烃插入规则，设计并合成了 48 个金酮和茚满酮衍生物。评估了它们对白色念珠菌、大肠杆菌和金黄色葡萄球菌的抑制活性。其中，三十种化合物表现出中等至优异的抗菌活性。方法：最大抑制圈为18 mm（化合物B15、B16和E7），MIC和MBC的最小值分别为15.625 μM（化合物A5和D2）和62.5 μM（化合物A6、A8和E7） . 结果：SAR表明，炔诺酮和茚满酮衍生物能强烈抑制革兰氏阳性菌的生长。吸电子基团或羟基的引入有利于活性。令人兴奋的是，本研究首次报道了具有抗菌活性的 3-苯基烯丙基苯并呋喃酮和 3-烯丙基萘酮骨架。选择化合物 A5 和 E7 与目标 MetRS (PBD: 7WPI) 和 PBP (PDB: 6C3K) 进行分子对接研究，以确定活性位点的结合相互作用。结论：在此基础上，对化合物的理化和药理性质进行了预测和分析。讨论了
• Design, synthesis, molecular docking and biological studies of some novel pyrrolidine-triazole-aurone hybrids against digestive enzymes
  作者：Sanjeev Kumar、Ekta Lathwal、Bhavna Saroha、Gourav Kumar、Arpana Bhardwaj、Poonam Bishnoi、Manishita Rani、Neera Raghav、Ramesh Kumar、Suresh Kumar

  DOI：10.1007/s11164-023-05221-1

  日期：2024.3

  effects on these enzymes as both trypsin and amylase were activated, but a significant inhibition was achieved for the lipase enzyme. Upon examining the binding energies of the synthesized compounds with the enzymes, it was observed that the experimental findings partially aligned with the docking results. These in vitro and in silico results of these hybrid aurones against digestive enzymes, signify their

  在这项工作中，我们成功设计并合成了一些新型吡咯烷-三唑-橙酮杂化物的文库，即 ( Z )-2-亚苄基-6-((1-(2-(吡咯烷-1-基)乙基)-1 H -1,2,3-三唑-4-基)甲氧基)苯并呋喃-3(2H ) -酮衍生物5(ak)。所有合成的杂化橙酮的结构均根据光谱（FT-IR、1 H NMR、13 C NMR）和 HRMS 数据得到确认。在生物学研究中，分析了合成化合物对消化酶、淀粉酶、脂肪酶和胰蛋白酶的影响。这些化合物对这些酶表现出不同的影响，因为胰蛋白酶和淀粉酶都被激活，但对脂肪酶具有显着的抑制作用。在检查合成化合物与酶的结合能时，观察到实验结果与对接结果部分一致。这些杂种橙酮对抗消化酶的体外和计算机结果表明它们作为抗炎和抗肥胖剂的潜力。
• Synthesis and Biological Activities of 6-Hydroxyaurone Derivatives
  作者：Yong-Tuan Bao、Min Zhang、Ting Li、Hui-Feng Xiao、Ting Zhao、Xiao-Hua Xu、Liu-Qing Yang

  DOI：10.1002/jhet.2497

  日期：2016.3

  A series of 6‐hydroxyaurone derivatives were synthesized in satisfactory yields and characterized by IR, 1H NMR, 13C NMR, and HRMS or elemental analysis. The structure of compound 3e was further confirmed by X‐ray crystal analysis. Bioassay results indicated that some of the target compounds displayed moderate herbicidal activity against the dicotyledonous plant Brassica campestris L. at 100 µg·mL−1, and some compounds also showed significant antiproliferative activity against tumor cell lines Hela, HepG‐2, and MCF‐7.