tert-butyl(2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)vinyl)phenoxy)dimethylsilane | 1067880-35-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl(2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)vinyl)phenoxy)dimethylsilane
• 英文别名: Tert-butyl-[2-methoxy-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]-dimethylsilane
• CAS: 1067880-35-6
• 化学式: C₂₄H₃₄O₅Si
• 分子量: 430.616
• InChiKey: YMMIJTLQYCRFCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.17
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl(2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)vinyl)phenoxy)dimethylsilane 在 甲醇 、 potassium carbonate 作用下， 反应 12.0h， 以94%的产率得到isocombretastatin A4
  参考文献：
  名称：

  ISO CA-4 AND ANALOGUES THEREOF AS POTENT CYTOTOXIC AGENTS INHIBITING TUBULINE POLYMERIZATION

  摘要：

  这项发明涉及公式（I）的化合物，其中：R1、R2和R3分别是一个甲氧基基团，该基团可以选择性地被一个或多个氟原子取代；R4是一个氢原子；R5和R6相同，每个代表一个氢或氟原子；A是从包括芳基和杂环基团在内的一组环中选择的，其中这些基团可以被取代。

  公开号：

  US20100129471A1
• 作为产物：
  描述：

  2-(叔丁基二甲基甲硅烷基氧基)-4-溴苯甲醚 在 重铬酸吡啶 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 tert-butyl(2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)vinyl)phenoxy)dimethylsilane
  参考文献：
  名称：

  Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions

  摘要：

  [3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn (OAc)(3) mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47 mu M, and compound 5p exhibted highest activity on HeLa cells with IC50 vaule of 2.32 mu M. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochemistry studies and cell cycle distribution analysis indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, molecular docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.048

文献信息

• DIHYDRO-ISO-CA-4 AND ANALOGUES: POTENT CYTOTOXICS, INHIBITORS OF TUBULIN POLYMERIZATION
  申请人：Alami Mouâd

  公开号：US20110160228A1

  公开（公告）日：2011-06-30

  The present invention relates to compounds of formula (I) below in which: —R 1 and R 3 represent, independently of one another, a methoxy group optionally substituted by one or more fluorine atoms, —R 2 and R 4 represent, independently of one another, a hydrogen atom or a methoxy group optionally substituted by one or more fluorine atoms, —A represents a ring chosen from the group comprising aryl and heteroaryl groups, said ring possibly being substituted by or fused to a heterocycle, —X represents a nitrogen atom or a CH group, and —Z 1 represents a hydrogen atom or a halogen atom, preferably fluorine, and —Z 2 represents a hydrogen atom, a halogen atom, preferably fluorine, a C 1 to C 4 alkyl group, an aryl group or a —CN, —SO 2 NR 12 R 13 , —SO 2 R 9 , —COOR 15 or —COR 15 group, and also to the pharmaceutically acceptable salts thereof, the isomers thereof and the prodrugs thereof.

  本发明涉及以下式（I）的化合物，其中：-R1和R3分别独立地表示一个甲氧基，该甲氧基可以被一个或多个氟原子取代，-R2和R4分别独立地表示一个氢原子或一个甲氧基，该甲氧基可以被一个或多个氟原子取代，-A表示从含有芳基和杂环芳基的群中选择的一个环，该环可能被一个杂环取代或融合，-X表示一个氮原子或一个CH基团，-Z1表示一个氢原子或一个卤原子，优选氟，-Z2表示一个氢原子，一个卤原子，优选氟，一个C1到C4烷基，一个芳基或一个-CN，-SO2NR12R13，-SO2R9，-COOR15或-COR15基团，以及其在药学上可接受的盐，其异构体和其前药。
• Exploring Diverse-Ring Analogues on Combretastatin A4 (CA-4) Olefin as Microtubule-Targeting Agents
  作者：Ming-Yu Song、Qiu-Rui He、Yi-Lin Wang、Hao-Ran Wang、Tian-Cheng Jiang、Jiang-Jiang Tang、Jin-Ming Gao

  DOI：10.3390/ijms21051817

  日期：——

  Combretastatin-4 (CA-4) as a tubulin polymerization inhibitor draws extensive attentions. However, due to its weak stability of cis-olefin and poor metabolic stability, structure modifications on cis-configuration are being performed. In this work, we constructed a series of novel CA-4 analogues with linkers on olefin containing diphenylethanone, cis-locked dihydrofuran, α-substituted diphenylethanone

  作为微管蛋白聚合抑制剂的Combretastatin-4（CA-4）引起了广泛关注。然而，由于其对顺式烯烃的弱稳定性和较差的代谢稳定性，正在对顺式构型进行结构修饰。在这项工作中，我们构建了一系列新型的CA-4类似物，其在含有二苯乙酮，顺式锁定的二氢呋喃，α-取代的二苯乙酮，环丁烷和环己烷的烯烃的顺式烯烃上具有连接基。通过SRB测定法测量所有类似物的细胞毒活性。其中，化合物6b是制备二苯乙酮类似物时的副产物，被发现是对HepG2细胞最有效的细胞毒剂，IC50值小于0.5μM。通过膜联蛋白V-FITC和碘化丙啶（PI）双重染色测试了6b的两种异构体诱导的细胞凋亡，通过PI染色分析将细胞停滞在G2 / M期，并通过免疫组化研究在HepG2细胞中破坏微管网络。此外，在体外微管蛋白聚合测定中，6b-（E）显示出对微管蛋白组装的剂量依赖性抑制作用。此外，分子对接研究表明，6b的两个异构体可以在类似于C
• <i>Iso</i>combretastatins A versus Combretastatins A: The Forgotten <i>iso</i>CA-4 Isomer as a Highly Promising Cytotoxic and Antitubulin Agent
  作者：Samir Messaoudi、Bret Tréguier、Abdallah Hamze、Olivier Provot、Jean-François Peyrat、Jordi Rodrigo De Losada、Jian-Miao Liu、Jérôme Bignon、Joanna Wdzieczak-Bakala、Sylviane Thoret、Joëlle Dubois、Jean-Daniel Brion、Mouâd Alami

  DOI：10.1021/jm900321u

  日期：2009.7.23

  Herein is reported a convergent synthesis of isocombretastatins A, a novel class of potent antitubulin agents. These compounds having a 1,1-diarylethylene scaffold constitute the simplest isomers of natural Z-combretastatins A that are easy to synthesize without need to control the Z-olefin geometry. The discovery of isoCA-4 with biological activities comparable to that of CA-4 represents a major progress in this field.
• Design and Synthesis of Tubulin and Histone Deacetylase Inhibitor Based on <i>iso</i>-Combretastatin A-4
  作者：Diana Lamaa、Hsin-Ping Lin、Lena Zig、Cyril Bauvais、Guillaume Bollot、Jérôme Bignon、Helene Levaique、Olivier Pamlard、Joelle Dubois、Mehdi Ouaissi、Martin Souce、Athena Kasselouri、François Saller、Delphine Borgel、Chantal Jayat-Vignoles、Hazar Al-Mouhammad、Jean Feuillard、Karim Benihoud、Mouad Alami、Abdallah Hamze

  DOI：10.1021/acs.jmedchem.8b00050

  日期：2018.8.9

  Designing multitarget drugs have raised considerable interest due to their advantages in the treatment of complex diseases such as cancer. Their design constitutes a challenge in antitumor drug discovery. The present study reports a dual inhibition of tubulin polymerization and HDAC activity. On the basis of 1,1-diarylethylenes (isoCA-4) and belinostat, a series of hybrid molecules was successfully designed and synthesized. In particular compounds, 5f and 5h were proven to be potent inhibitors of both tubulin polymerization and HDAC8 leading to excellent antiproliferative activity.