(Z)-2-(2'-amino-4'-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene | 519060-26-5

• 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)-2-(2'-amino-4'-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene
• 英文别名: 2'-NH2-CA4；2'-amino-3,4,4',5-tetramethoxy-(Z)-stilbene；5-methoxy-2-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]aniline
• CAS: 519060-26-5
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: XMMNPPLYAJJFPL-WAYWQWQTSA-N

物化性质

• 熔点：
  94.0-94.9 °C
• 沸点：
  496.3±45.0 °C(Predicted)
• 密度：
  1.163±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-2-(2'-amino-4'-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene 在 1-丙基磷酸酐 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成 2-amino-N-(5-methoxy-2-((Z)-3,4,5-trimethoxystyryl)phenyl)acetamide
  参考文献：
  名称：

  设计，合成和生物学评估衍生自康普他汀，二氢萘和苯并sub烯的母体血管破坏剂的水溶性氨基酸前药结合物。

  摘要：

  靶向肿瘤脉管系统代表了在癌症治疗中的一种有趣的治疗策略。为了发现具有改善的水溶性和潜在更高的生物利用度的新的血管破坏剂，合成了有效的氨基康他汀，氨基二氢萘和氨基苯甲sub烯类似物的各种氨基酸前药共轭物（AAPC）及其相应的水溶性盐酸盐。对这些化合物抑制微管蛋白聚合的能力以及对选定的人类癌细胞系的细胞毒性进行了评估。基于氨基的亲本抗癌药7、8、32（也称为KGP05）和33（也称为KGP156）在所有评估的细胞系中均显示出强大的细胞毒性（GI50 = 0.11-40nM），它们是微管蛋白聚合的强抑制剂（IC50 =0.62-1.5μM）。研究了各种前药缀合物及其相应的盐是否被亮氨酸氨基肽酶（LAP）切割。甘氨酸水溶性AAPC中有四个（16、18、44和45）显示LAP定量裂解，导致释放出高细胞毒性母体药物，而其他前药则观察到部分裂解（<10-90％）（ 15、17、24、38和39）。19枚

  DOI：

  10.1016/j.bmc.2016.01.007
• 作为产物：
  描述：

  4-甲氧基-2-硝基溴苄 在 sodium dithionite 、 sodium hydride 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 32.0h， 生成 (Z)-2-(2'-amino-4'-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents

  摘要：

  A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or C-C-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably functionalized arylaldehyde and an arylphosphonium salt followed by separation of the resultant F and Z-isomers. several of these nitrogen-modified CA4 derivatives (both amino and nitro) demonstrate significant inhibition of tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2'-Aminostilbenoid 7 and 2'-amino-3'-hydroxystilbenoid 29 proved to be the most active in this series. Both compounds, 7 and 29, have the potential for further pro-drug modification and development as vascular disrupting agents for treatment of solid tumor cancers and certain ophthalmological diseases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.12.033

文献信息

• Functionalized stilbene derivatives as improved vascular targeting agents
  申请人：——

  公开号：US20030149003A1

  公开（公告）日：2003-08-07

  Novel stilbenoid compounds and their prodrug forms are disclosed, which serve as potent vascular targeting agents useful for the treatment of solid tumor cancers and other diseases associated with unwanted neovascularization. The novel stilbenoid compounds are tubulin-binding stilbenoid analogs structurally related to combretastatin A-1 and combretastatin A-4. The prodrug forms serve as potent vascular targeting agents (VTAs) useful for the treatment of solid tumor cancers and diseases associated with retinal neovascularization.

  本发明揭示了一种新型的苯乙烯类化合物及其前药形式，其作为强效的血管靶向剂，可用于治疗实体肿瘤癌和其他与不需要的新生血管化有关的疾病。这些新型的苯乙烯类化合物是微管结合的苯乙烯类类似物，其结构与康布雷他斯汀A-1和康布雷他斯汀A-4有关。前药形式作为强效的血管靶向剂（VTAs），可用于治疗实体肿瘤癌和与视网膜新生血管化有关的疾病。
• 2-Amino and 2‘-Aminocombretastatin Derivatives as Potent Antimitotic Agents
  作者：Jang-Yang Chang、Ming-Fang Yang、Chi-Yen Chang、Chi-Ming Chen、Ching-Chuan Kuo、Jing-Ping Liou

  DOI：10.1021/jm060616k

  日期：2006.10.1

  A novel series of 2-amino and 2'-aminocombretastatin derivatives were synthesized and evaluated for antitumor activity. Several compounds had excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 11, 20, and 21 with IC50 values of 1.6, 1.7, and 1.8 mu M, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine and approximately as active as combretastatin A-4. They also displayed antiproliferative activity with an IC50 values ranging from 11 to 44 nM in a variety of human cell lines from different organs. Structure activity relationship information suggests that the NH2 substituent at the 2-position of either ring A or ring B in combretastatin molecular skeleton may play an important role in the bioactivity of this series of compounds.
• FUNCTIONALIZED STILBENE DERIVATIVES AS IMPROVED VASCULAR TARGETING AGENTS
  申请人：Oxigene, Inc.

  公开号：EP1438281A2

  公开（公告）日：2004-07-21
• EP1438281A4
  申请人：——

  公开号：EP1438281A4

  公开（公告）日：2006-04-26
• N-((3,4,5-TRIMETHOXYSTYRYL)ARYL)CINNAMAMIDE COMPOUNDS AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US20170240503A1

  公开（公告）日：2017-08-24

  The present invention provides a compound of general formula A, useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. [Formula should be entered here] General formula A where in B selected from aryl, heteroaryl and fused heteroaryl ring R and X selected from H, hydroxy, alkyl, alkoxy, prop-2-ynyloxy, allyloxy, halo, alkylhalides, alkoxy halides, nitro, amine.