(Z)-5-(4-ethoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene | 1015697-68-3

• 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: (Z)-5-(4-ethoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene
• 英文别名: (Z)-1-(3,4,5-trimethoxyphenyl)-2-(3-nitro-4-ethoxyphenyl)ethylene；5-[(Z)-2-(4-ethoxy-3-nitrophenyl)ethenyl]-1,2,3-trimethoxybenzene
• CAS: 1015697-68-3
• 化学式: C₁₉H₂₁NO₆
• 分子量: 359.379
• InChiKey: QGYLQSLHDNLZCV-SREVYHEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (Z)-5-(4-ethoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 3.0h， 以90%的产率得到2-ethoxy-5-(3,4,5-trimethoxyphenethyl)benzenamine
  参考文献：
  名称：

  Design, synthesis and anti-proliferative effects in tumor cells of new combretastatin A-4 analogs

  摘要：

  A total of 11 novel combretastatin A-4 (CA-4) analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes: (i) hydrogenated derivatives, (ii) ethoxyl derivatives, (iii) amino derivatives and (iv) pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure-activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2015.05.003
• 作为产物：
  描述：

  4-羟基-3-硝基苯甲醛 在 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.17h， 生成 (Z)-5-(4-ethoxy-3-nitrostyryl)-1,2,3-trimethoxybenzene
  参考文献：
  名称：

  Design, synthesis and anti-proliferative effects in tumor cells of new combretastatin A-4 analogs

  摘要：

  A total of 11 novel combretastatin A-4 (CA-4) analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes: (i) hydrogenated derivatives, (ii) ethoxyl derivatives, (iii) amino derivatives and (iv) pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure-activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2015.05.003

文献信息

• PREPARATION AND THE USE OF ETHOXY COMBRETASTATINS AND THEIR PRODRUGS
  申请人：Shen Weiping

  公开号：US20090170956A1

  公开（公告）日：2009-07-02

  The invention disclosed a total synthesis process of novel ethoxy combretastatins and their prodrugs. Combretastatins are chemically modified by ethoxy substituted on the 4′-position of their B aryl ring and are converted to be their soluble prodrugs of phosphate or their inner salt of phosphorylcholine by modifying the hydroxyl on the 3′-position of their B aryl ring. Similarly, 3′-amino combretastatin is 4′-ethoxy chemically modified and further side chain of amino acid can be introduced to the amino to form soluble prodrug of amino acidamide. The structure of the said compound is showed as formula (I). Ethoxy combretastatins possess potent tubulin polymerization inhibitory activity and can be used for the treatment of inhibiting tumor or neovascular.

  该发明揭示了一种新型乙氧基康柏他静的全合成过程及其前药。康柏他静通过在其B芳香环的4'-位上进行乙氧基取代进行化学修饰，并通过修改其B芳香环的3'-位上的羟基转化为其磷酸盐的可溶性前药或磷酰胆碱的内盐。类似地，3'-氨基康柏他静经过4'-乙氧基化学修饰，进一步可以引入氨基酸的侧链到氨基上形成氨基酸酰胺的可溶性前药。所述化合物的结构如化学式(I)所示。乙氧基康柏他静具有强大的微管聚合抑制活性，可用于治疗抑制肿瘤或新生血管的情况。
• Combretastatin A-4 and Derivatives: Potential Fungicides Targeting Fungal Tubulin
  作者：Zhong-lin Ma、Xiao-jing Yan、Lei Zhao、Jiu-jiu Zhou、Wan Pang、Zhen-peng Kai、Fan-hong Wu

  DOI：10.1021/acs.jafc.5b05119

  日期：2016.2.3

  configuration and hydroxyl group in combretastatin A-4 are crucial to the antifungal effect. Molecular modeling indicated the binding sites of combretastatin A-4 and carbendazim on fungal tubulin are totally different. The bioactivity of combretastatin A-4 and its derivatives against carbendazim-resistant strains was demonstrated in this study. The results provide a new approach for fungicide discovery and

  Combretastatin A-4首先从非洲柳树Combretum caffrum中分离出来，是医学上的微管蛋白聚合抑制剂。在本研究中，它首先被假定为潜在的针对真菌微管蛋白的杀菌剂，可用于控制植物病害。合成了Combretastatin A-4及其衍生物，并对其进行了茄枯萎病和稻瘟病菌的抗药性试验。几种化合物的EC 50值类似于或优于异丙基硫烷的EC 50值，后者广泛用于水稻疾病控制。结构-活性关系研究表明顺式康他汀A-4的构型和羟基对于抗真菌作用至关重要。分子建模表明，康布雷他汀A-4和多菌灵在真菌微管蛋白上的结合位点完全不同。这项研究证明了康普他汀A-4及其衍生物对多菌灵耐药菌株的生物活性。结果为杀菌剂发现和杀菌剂抗性管理提供了一种新方法。
• AMINO-COMBRETASTATIN DERIVATIVE AND USE THEREOF
  申请人：YIWUHUAYAO PHARMACEUTICAL TECHNOLOGY CO., LTD

  公开号：EP4245750A1

  公开（公告）日：2023-09-20

  Disclosed is an amino-combretastatin derivative, and in particular a compound represented by general formula (I), a pharmaceutically acceptable salt thereof, a hydrate thereof, or a hydrate of the pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof, and an isomer thereof. In general formula (I), R1 is selected from a C1-C3 alkyl or a C1-C3 haloalkyl, and R2 and R3 are respectively and independently selected from a C1-C6 alkyl, a C1-C6 haloalkyl or a C1-C6 alcohol group. The present invention also relates to the use of such compounds in the preparation of drugs for the treatment of diseases caused by abnormal neovascularization, and tubulin aggregation inhibitors.

  本发明公开了一种氨基山椒素衍生物，特别是由通式(I)表示的化合物、其药学上可接受的盐、其水合物、其药学上可接受的盐的水合物、其溶剂化合物或其药学上可接受的盐的溶剂化合物以及其异构体。在通式(I)中，R1选自C1-C3烷基或C1-C3卤代烷基，R2和R3分别独立地选自C1-C6烷基、C1-C6卤代烷基或C1-C6醇基。本发明还涉及这些化合物在制备用于治疗由异常新生血管引起疾病药物中的用途，以及作为微管聚集抑制剂的应用。
• THE PREPARTION AND THE USE OF ETHOXY COMBRETASTATINS AND THEIR PRODRUGS
  申请人：Zhejiang Dade Pharmaceutical Group Co., Ltd.

  公开号：EP2065358B1

  公开（公告）日：2015-07-08
• ETHOXY DIPHENYL ETHANE DERIVATES, PREPARATION PROCESSES AND USES THEREOF
  申请人：Shanghai Ecust Biomedicine Co., Ltd

  公开号：EP2351730B1

  公开（公告）日：2014-07-30