4-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2(5H)-furanone | 446044-05-9

• 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: 4-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2(5H)-furanone
• 英文别名: 3-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-2H-furan-5-one
• CAS: 446044-05-9
• 化学式: C₂₀H₂₀O₆
• 分子量: 356.375
• InChiKey: IBGFIBLQTNLWCF-UHFFFAOYSA-N

物化性质

• 熔点：
  139-141 °C
• 沸点：
  549.2±50.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2(5H)-furanone 在 二异丁基氢化铝 、 三氯化磷 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 3-(4-Methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)furan-2-carbaldehyde
  参考文献：
  名称：

  Synthesis and Cytotoxic Evaluation of Combretafurans, Potential Scaffolds for Dual-Action Antitumoral Agents

  摘要：

  We have synthesized rigid analogues of combretastatin bearing a furan ring in place of the olefinic bridge. These compounds are cytotoxic at nanomolar concentrations in neuroblastoma cells, display a similar structure- activity relationship compared to combretastatin A4, and inhibit tubulin polymerization. We also show that the furan ring can be further functionalized. Thus, it is possible that combretafurans could act as scaffolds for the development of dual-action antitumoral agents.

  DOI：

  10.1021/jm060621o
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 在 4 A molecular sieve 、 TEA 、 对甲苯磺酸 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成 4-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2(5H)-furanone
  参考文献：
  名称：

  3,4-二芳基-2（5H）-呋喃酮的合成和细胞毒性。

  摘要：

  合成了一系列3,4-二芳基-2（5H）-呋喃酮衍生物，并评估了其在小部分癌细胞系中的细胞毒性。该系列的10种化合物中有4种，例如3-（3,4,5-三甲氧基苯基）-4-（4-甲氧基苯基）-，3-（3,4,5-三甲氧基苯基）-4-（3-羟基-4-甲氧基苯基）-，3-（3,4,5-三甲氧基苯基）-4-（3-氨基-4-甲氧基苯基）-和3-（3,4,5-三甲氧基苯基）-4-（2-发现在大多数测试的细胞系中，萘基）-2（5H）-呋喃酮具有强的细胞毒活性，ED50值小于20 nM。

  DOI：

  10.1016/s0960-894x(01)00831-9

文献信息

• Synthesis and Cytotoxicity of 3,4-Diaryl-2(5H)-furanones
  作者：Yong Kim、Nguyen-Hai Nam、Young-Jae You、Byung-Zun Ahn

  DOI：10.1016/s0960-894x(01)00831-9

  日期：2002.2

  4-diaryl-2(5H)-furanone derivatives were synthesized and evaluated for their cytotoxicity in a small panel of cancer cell lines. Four out of 10 compounds in this series, for example 3-(3,4,5-trimethoxyphenyl)-4-(4-methoxyphenyl)-, 3-(3,4,5-trimethoxyphenyl)-4-(3-hydroxy-4-methoxyphenyl)-, 3-(3,4,5-trimethoxyphenyl)-4-(3-amino-4-methoxyphenyl)-, and 3-(3,4,5-trimethoxyphenyl)-4-(2-naphthyl)-2(5H)-furanones

  合成了一系列3,4-二芳基-2（5H）-呋喃酮衍生物，并评估了其在小部分癌细胞系中的细胞毒性。该系列的10种化合物中有4种，例如3-（3,4,5-三甲氧基苯基）-4-（4-甲氧基苯基）-，3-（3,4,5-三甲氧基苯基）-4-（3-羟基-4-甲氧基苯基）-，3-（3,4,5-三甲氧基苯基）-4-（3-氨基-4-甲氧基苯基）-和3-（3,4,5-三甲氧基苯基）-4-（2-发现在大多数测试的细胞系中，萘基）-2（5H）-呋喃酮具有强的细胞毒活性，ED50值小于20 nM。
• Mucochloric Acid: A Useful Synthon for the Selective Synthesis of 4-Aryl-3-chloro-2(5H)-furanones, (Z)-4-Aryl-5-[1-(aryl)methylidene]-3-chloro-2(5H)-furanones and 3,4-Diaryl-2(5H)-furanones
  作者：Fabio Bellina、Chiara Anselmi、Francesca Martina、Renzo Rossi

  DOI：10.1002/ejoc.200300097

  日期：2003.6

  4-Dichloro-2(5H)-furanone, which has been prepared efficiently from mucochloric acid, has been transformed selectively into 4-aryl-3-chloro-2(5H)-furanones either by Suzuki- or Stille-type reactions. These monochloro derivatives have been used as precursors either to (Z)-4-aryl-5-[1-(aryl)methylidene]-3-chloro-2(5H)-furanones, including naturally occurring rubrolide M, or to unsymmetrical 3,4-diaryl-2(5H)-furanones

  由粘氯酸有效制备的3,4-二氯-2（5 H）-呋喃酮已通过Suzuki-或Stille-选择性地转化为4-芳基-3-氯-2（5 H）-呋喃酮类型反应。这些一氯衍生物已被用作（Z）-4-芳基-5- [1-（芳基）亚甲基] -3-氯-2（5 H）-呋喃酮的前体，包括天然存在的罗布洛尔M，或不对称的前体。 3，4-二芳基-2（5 H）-呋喃酮。约2（5 H已经发现，如此制备的呋喃酮衍生物在体外对NCI三细胞系面板表现出显着的细胞毒性活性，但是对NCI人肿瘤60细胞系面板的细胞毒性有限。（©Wiley-VCH Verlag GmbH＆Co.KGaA，69451 Weinheim，Germany，2003）
• Photostability and Antiproliferative Activity of Furan Analogues of Combretastatin A-4
  作者：Alexander Scherbakov、Alexey V. Zakharov、Ekaterina I. Mikhaevich、Diana I. Salnikova、Anton V. Yadykov、Arina A. Kozhevnikova、Valerii Z. Shirinian

  DOI：10.1021/acs.chemrestox.2c00204

  日期：2022.11.21

  Cancer is one of the most serious health problems that usually require heavy medical treatment. It is important to ensure that no additional burden is placed on patients due to the modes of administration and/or poor quality of pharmaceuticals. In this regard, understanding, quantifying, and improving the photostability (resistance to UV light or sunlight) of drugs is among the important elements that can improve the patient’s quality of life. In this work, the photochemical properties of a wide range of furanone analogues of combretastatin A-4 and their antiproliferative activity against A-431 epidermoid carcinoma cells were studied in a search for compounds with improved photostability and antiproliferative activity. It was found that the incorporation of an arylidene moiety led to a significant improvement in photostability, while the antiproliferative activity strongly depends on the nature of the aryl residue in the arylidene moiety. The high photostability of arylidenes was achieved due to the delocalization of the central double bond of the 1,3,5-hexatriene system, which limited the 6π-electrocyclization. The best results in terms of antiproliferative activity were obtained for thiophene arylidene (IC50 = 0.6 μM) and 3,4-diarylfuran (IC50 = 0.047 μM). The obtained results address the lack of data available now in scientific literature on the photodegradation of combretastatin A-4 analogues and should be taken into account in studies of the side effects of pharmaceuticals based on them.

  癌症是最严重的健康问题之一，通常需要大量的药物治疗。必须确保不因给药方式和/或药品质量差而给患者造成额外负担。在这方面，了解、量化和改善药物的光稳定性（对紫外线或阳光的耐受性）是提高患者生活质量的重要因素之一。在这项工作中，为了寻找具有更好光稳定性和抗增殖活性的化合物，研究了多种康瑞他汀 A-4 呋喃酮类似物的光化学特性及其对 A-431 表皮样癌细胞的抗增殖活性。研究发现，加入亚芳基后，光稳定性显著提高，而抗增殖活性则在很大程度上取决于亚芳基中芳基残基的性质。1,3,5-己三烯体系中心双键的去局域化限制了 6π 电环化，从而使芳基烯具有较高的光稳定性。在抗增殖活性方面，噻吩亚芳基（IC50 = 0.6 μM）和 3,4-二芳基呋喃（IC50 = 0.047 μM）的结果最好。这些结果解决了目前科学文献中缺乏有关考布他丁 A-4 类似物光降解数据的问题，在研究基于这些类似物的药物的副作用时应加以考虑。
• Novel hybrids of fluconazole and furanones: Design, synthesis and antifungal activity
  作者：Hanumant B. Borate、Sangmeshwer P. Sawargave、Subhash P. Chavan、Mohan A. Chandavarkar、Ramki Iyer、Amit Tawte、Deepali Rao、Jaydeep V. Deore、Ananada S. Kudale、Pankaj S. Mahajan、Gopinath S. Kangire

  DOI：10.1016/j.bmcl.2011.06.022

  日期：2011.8

  During our efforts to develop new antifungal agents, a number of hybrid molecules containing furanones and fluconazole pharmacophores were designed and synthesized. The new chemical entities thus synthesized were tested for their potential as antifungal agents against various fungal strains and it was observed that the compounds with general structure 7 were potent inhibitors of Candida albicans ATCC 24433, Candida glabrata ATCC 90030, Candida tropicalis ATCC 750 and Candida neoformans ATCC 34664 while the fluconazole analogues 12 exhibited antifungal activity against Candida albicans ATCC 24433 and Candida glabrata ATCC 90030. The structure-activity relationship for these compounds is discussed. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures to obtain molecules suitable for development as antifungal drugs. (C) 2011 Elsevier Ltd. All rights reserved.
• Photoswitching off the Antiproliferative Activity of Combretastatin A-4 Analogues
  作者：Anton V. Yadykov、Alexander M. Scherbakov、Victoria V. Trofimova、Andrey G. Lvov、Ashot I. Markosyan、Igor V. Zavarzin、Valerii Z. Shirinian

  DOI：10.1021/acs.orglett.9b03780

  日期：2019.12.6

  The photostability and antiproliferative activity of combretastatin A-4 (CA-4) analogues against human epidermoid carcinoma cells A-431 were studied. For the first time, it was shown that UV or sunlight irradiation of furanone analogues of CA-4 results in a photorearrangement giving products with relatively low antiproliferative activity. The observed ability of this series CA-4 to the photodegradation can be used for the design of a new class of drug candidates with high selectivity to cancer cells.