(Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one | 139276-16-7

• 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-benzylidene-6-hydroxybenzofuran-3(2H)-one
• 英文别名: 6-hydroxy-2-(phenylmethylene)-3(2H)-benzofuranone；6-hydroxyaurone；(2Z)-2-benzylidene-6-hydroxy-1-benzofuran-3(2H)-one；(2Z)-2-benzylidene-6-hydroxy-1-benzofuran-3-one
• CAS: 139276-16-7
• 化学式: C₁₅H₁₀O₃
• mdl: MFCD04145101
• 分子量: 238.243
• InChiKey: KDGIFQNPGMXJCY-ZSOIEALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 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：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  (Z)-2-benzylidene-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-Benzyl-6-methoxy-cumaranon
  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 水 、 sodium methylate 、 zinc(II) chloride 作用下， 生成 (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one
  参考文献：
  名称：

  三氟甲基化金龙酮衍生物的合成，表征和抗癌作用

  摘要：

  合成了一系列三氟甲基化的金酮衍生物，并通过单晶X射线分析确定了6-羟基-4-三氟甲基化的金酮的结构。使用5-氟尿嘧啶作为阳性对比药物，通过标准MTT方法体外评估了它们对白细胞增多症（HL-60）和大肠腺癌（HT-29）的抗癌活性。结果表明，所有（Z）-三氟甲基化的金酮衍生物均具有潜在的抗癌活性。

  DOI：

  10.1002/jhet.1969

文献信息

• Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase
  作者：Oksana V. Muzychka、Oleksandr L. Kobzar、Antonina V. Popova、Mykhaylo S. Frasinyuk、Andriy I. Vovk

  DOI：10.1016/j.bmc.2017.04.048

  日期：2017.7

  study, a number of A- and B-ring carboxylated aurone derivatives were synthesized and evaluated for their ability to inhibit xanthine oxidase in vitro. According to the results obtained, two different ranges of inhibitory activity were observed. The aurones with carboxylic acid group at the 4′-position of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar

  黄嘌呤氧化酶是治疗高尿酸血症和痛风的潜在靶标。在这项研究中，合成了许多A环和B环羧化的金酮衍生物，并评估了它们在体外抑制黄嘌呤氧化酶的能力。根据获得的结果，观察到两个不同范围的抑制活性。发现在B环的4'-位具有羧酸基团的金黄色素是该酶的有效抑制剂，其IC 50值在低微摩尔范围内。这些化合物的作用比在6-位具有羧基甲氧基的A-环修饰的金酮的作用高约50倍。使用分子对接计算解释了黄嘌呤氧化酶活性位点中羧化金氧烷的结合方式。
• Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity
  作者：Marta P. Carrasco、Ana S. Newton、Lídia Gonçalves、Ana Góis、Marta Machado、Jiri Gut、Fátima Nogueira、Thomas Hänscheid、Rita C. Guedes、Daniel J.V.A. dos Santos、Philip J. Rosenthal、Rui Moreira

  DOI：10.1016/j.ejmech.2014.04.076

  日期：2014.6

  were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2

  通过苯并呋喃酮和适当取代的苯甲醛的直接醛醇缩合反应合成了包含44个不同取代的金酮衍生物的文库。引入了使用钯催化方案的微波增强合成，作为扩展金质支架周围化学空间的有力策略。另外，还制备了在环A处含有7-氨基甲基-6-羟基取代图案的曼尼希碱衍生物。针对耐氯喹的恶性疟原虫W2菌株进行筛选，鉴定出具有IC 50的新型金质值在低微摩尔范围内。最有效的化合物包含一个碱性部分，具有在疟原虫的酸性消化液中积累的能力。然而，这些金黄色素均未显示出对血zo素形成和falcipain-2的显着活性，falcipain-2是在恶性疟原虫感染的血液阶段表达的两个经过验证的靶标，并在该寄生虫的消化液中起作用。总的来说，这项研究突出了（i）金氧烷作为使用钯催化方法快速递送先导化合物进行进一步优化的合成程序平台的有用性，以及（ii）新型金酮衍生物作为有前景的抗疟疾化合物的潜力。
• Azaaurones as Potent Antimycobacterial Agents Active against MDR‐ and XDR‐TB
  作者：André Campaniço、Marta P. Carrasco、Mathew Njoroge、Ronnett Seldon、Kelly Chibale、João Perdigão、Isabel Portugal、Digby F. Warner、Rui Moreira、Francisca Lopes

  DOI：10.1002/cmdc.201900289

  日期：2019.8.20

  isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm, whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC99 values ranging from 0.4 to 2.0 μm. In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant

  在此，我们报告了针对结核分枝杆菌的一个小型金黄色素及其等排性对映体，氮卓酮和N-乙酰基氮卓酮的文库的筛选。发现Aurones在20μm处无活性，而氮杂Aauaurones和N-乙酰基氮杂Aauaurones则是最有效的化合物，其中九种衍生物的MIC99值在0.4至2.0μm之间。另外，发现几种N-乙酰氮杂金龙酮对多药耐药（MDR）和广泛耐药（XDR）临床结核分枝杆菌具有活性。这些化合物的抗分枝杆菌的作用机理尚待确定。但是，一项初步的机理研究证实，它们不会抑制分枝杆菌细胞色素bc1复合物。此外，微粒体的代谢稳定性和代谢物鉴定研究表明，N-乙酰基氮杂金龙酮被脱乙酰化为其对应的氮杂金龙酮。总体而言，这些结果表明，氮金龙酮及其N-乙酰基对应物代表了能够抑制结核分枝杆菌生长的化学型工具箱中的一个新条目。
• 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 :
• Investigation of Binding-Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors
  作者：Romain Haudecoeur、Aurélie Gouron、Carole Dubois、Hélène Jamet、Mark Lightbody、Renaud Hardré、Anne Milet、Elisabetta Bergantino、Luigi Bubacco、Catherine Belle、Marius Réglier、Ahcène Boumendjel

  DOI：10.1002/cbic.201402003

  日期：2014.6.16

  A lighter future: Aurones have been identified as inhibitors of melanin biosynthesis. In this study, 24 aurones were evaluated on mushroom and bacterial tyrosinases (TyM and TyB). The compounds behaved as inhibitors, substrates, or activators of both enzymes. Our results highlight similarities and differences in behavior between TyM and TyB with the same set of molecules.

  更光明的未来： Aurones已被确定为黑色素生物合成的抑制剂。在这项研究中，对蘑菇和细菌酪氨酸酶（TyM和TyB）上的24种金质进行了评估。该化合物充当两种酶的抑制剂，底物或激活剂。我们的结果强调了在同一分子下TyM和TyB之间行为的异同。