(E)-3-(3-fluoro-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid | 853794-91-9

• 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: (E)-3-(3-fluoro-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid
• 英文别名: (E)-3-(3-fluoro-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enoic acid
• CAS: 853794-91-9
• 化学式: C₁₉H₁₉FO₆
• 分子量: 362.355
• InChiKey: CYQDGQQLSPXEGM-NTUHNPAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-fluoro-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid 在 吡啶 、 ammonium hydroxide 、 氯化亚砜 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (E)-3-(3-fluoro-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enenitrile
  参考文献：
  名称：

  Novel cyanocombretastatins as potent tubulin polymerisation inhibitors

  摘要：

  A series of novel cyanocombretastatins bearing a 3,4,5-trimethoxyphenyl moiety combined with a variety of substituted phenyl rings, were synthesised and their antitumour activity was evaluated. The Z-cyanocombretastatins were synthesised in a one-step protocol in high purity and yield. Fluoro, bromo, iodo, and derivatives with boronic acid and an ethyne function at meta position of the B ring were synthesised. In vitro MTT bioassays against human chronic myelogenous leukaemia (K562) and transfected breast adenocarcinoma (MDA NQO1) cell lines, revealed promising IC50 inhibitory values in nanomolar range (<50 nM). Introduction of a nitrile function on the olefinic bond not only increased the cytotoxicity of the less active Z-isomers but rendered the analogues as moderate to potent inhibitors of tubulin polymerisation comparable to that of CA-4 (IC50 = 2.2 mu M). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.089
• 作为产物：
  描述：

  3-氟-4-甲氧基苯甲醛 、 3,4,5-三甲氧基苯乙酸 在 乙酸酐 、 三乙胺 作用下， 反应 3.0h， 以42%的产率得到(E)-3-(3-fluoro-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid
  参考文献：
  名称：

  康他汀A4系列中的新抗微管蛋白衍生物：合成和生物学评估。

  摘要：

  为了改善水溶性和稳定双键的顺式构型，合成了两种康普他汀A4衍生物（丙烯酰胺=羧酰胺和氨基甲酸酯）。评估了它们对MCF-7，KB-3-1和IGROV人癌细胞系的细胞毒性作用，以及它们对微管蛋白聚合的抑制活性。将结果与选择的羧酰胺1的结果进行比较。在羧酰胺系列的两个试验中均观察到了强力抑制作用，特别是对于带有氟基团的化合物4d替代了CA4的3-羟基。相反，大多数氨基甲酸酯要么是无活性的，要么仅表现出中等的细胞毒性。有趣的是，尽管该化合物完全没有抗微管蛋白活性，但在MCF-7细胞上测得亚微摩尔IC（50）为6g。

  DOI：

  10.1016/j.bmc.2005.02.039

文献信息

• New antitubulin derivatives in the combretastatin A4 series: synthesis and biological evaluation
  作者：Christine Borrel、Sylviane Thoret、Xavier Cachet、Daniel Guénard、François Tillequin、Michel Koch、Sylvie Michel

  DOI：10.1016/j.bmc.2005.02.039

  日期：2005.6

  carboxamide 1, chosen as reference. Potent inhibitions were observed on both tests in the carboxamide series, particularly for compound 4d bearing a fluorine group in replacement of the 3-hydroxyl of CA4. In contrast, most of the carbamates were either inactive or displayed only moderate cytotoxicities. Interestingly, a submicromolar IC(50) was measured on MCF-7 cells for 6g, although this compound was totally

  为了改善水溶性和稳定双键的顺式构型，合成了两种康普他汀A4衍生物（丙烯酰胺=羧酰胺和氨基甲酸酯）。评估了它们对MCF-7，KB-3-1和IGROV人癌细胞系的细胞毒性作用，以及它们对微管蛋白聚合的抑制活性。将结果与选择的羧酰胺1的结果进行比较。在羧酰胺系列的两个试验中均观察到了强力抑制作用，特别是对于带有氟基团的化合物4d替代了CA4的3-羟基。相反，大多数氨基甲酸酯要么是无活性的，要么仅表现出中等的细胞毒性。有趣的是，尽管该化合物完全没有抗微管蛋白活性，但在MCF-7细胞上测得亚微摩尔IC（50）为6g。
• [EN] SUBSTITUTED 4-BETA-ACRYLAMIDOPODOPHYLLOTOXIN CONGENERS AS ANTITUMOUR ANTIBIOTICS AND THE PROCESS FOR PREPARATION THEREOF<br/>[FR] CONGÉNÈRES DE 4-BÊTA-ACRYLAMIDOPODOPHYLLOTOXINE SUBSTITUÉS EN TANT QU'ANTIBIOTIQUES ANTITUMORAUX ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2012063250A1

  公开（公告）日：2012-05-18

  The present invention provides compounds of general formula (3) as useful potential antitumour agents against human cancer cell lines. The present invention further provides a process for the synthesis of 4β-acrylamidopodophyllotoxin congeners of general formula (3). wherein R and R1 are an aryl group and R is selected from 3, 4, 5-trimethoxyphenyl or 2-methoxy phenyl and R1 is selected from the group consisting of 4-hydroxy-3- methoxyphenyl, 3-hydroxy-4-methoxyphenyl, 4-fluoro-3-methoxyphenyl, 3-fluoro-4- methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 4-hydroxy-3- nitrophenyl, 4-methoxy-3-nitrophenyl, 4-nitrophenyl, 3-nitrophenyl, 2-nitro phenyl, 4- methoxyphenyl, 3-methoxyphenyl and 4-hydroxyphenyl.

  本发明提供了一种通式（3）的化合物，作为潜在的抗人类癌细胞系肿瘤药物。本发明还提供了一种合成通式（3）的4β-丙烯酰胺基青叶子碱类似物的方法。其中R和R1是芳基基团，R选自3,4,5-三甲氧基苯基或2-甲氧基苯基，R1选自4-羟基-3-甲氧基苯基、3-羟基-4-甲氧基苯基、4-氟-3-甲氧基苯基、3-氟-4-甲氧基苯基、2-氟-5-甲氧基苯基、2-氟-4-甲氧基苯基、4-羟基-3-硝基苯基、4-甲氧基-3-硝基苯基、4-硝基苯基、3-硝基苯基、2-硝基苯基、4-甲氧基苯基、3-甲氧基苯基和4-羟基苯基。
• SUBSTITUTED 4-BETA-ACRYLAMIDOPODOPHYLLOTOXIN CONGENERS AS ANTITUMOUR ANTIBIOTICS AND THE PROCESS FOR PREPARATION THEREOF
  申请人：Ahmed Kamal

  公开号：US20130225672A1

  公开（公告）日：2013-08-29

  The present invention provides compounds of general formula (3) as useful potential antitumour agents against human cancer cell lines. The present invention further provides a process for the synthesis of 4β-acrylamidopodophyllotoxin congeners of general formula (3), wherein R and R1 are an aryl group and R is selected from 3,4,5-trimethoxyphenyl or 2-methoxy phenyl and R1 is selected from the group consisting of 4-hydroxy-3-methoxyphenyl, 3-hydroxy-4-methoxyphenyl, 4-fluoro-3-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 4-hydroxy-3-nitrophenyl, 4-methoxy-3-nitrophenyl, 4-nitrophenyl, 3-nitrophenyl, 2-nitro phenyl, 4-methoxyphenyl, 3-methoxyphenyl and 4-hydroxyphenyl.

  本发明提供通式（3）的化合物，作为潜在的抗人类癌细胞系的抗肿瘤剂。本发明还提供一种合成通式（3）的4β-丙烯酰胺基淫羊藿毒素同系物的方法，其中R和R1是芳基，R选自3,4,5-三甲氧基苯基或2-甲氧基苯基，R1选自4-羟基-3-甲氧基苯基、3-羟基-4-甲氧基苯基、4-氟-3-甲氧基苯基、3-氟-4-甲氧基苯基、2-氟-5-甲氧基苯基、2-氟-4-甲氧基苯基、4-羟基-3-硝基苯基、4-甲氧基-3-硝基苯基、4-硝基苯基、3-硝基苯基、2-硝基苯基、4-甲氧基苯基、3-甲氧基苯基和4-羟基苯基的群。
• STILBENE COMPOUNDS FOR USE IN THE TREATMENT OF TUMOUR AND EYE DISEASES
  申请人：Guangzhou AnHao Pharmaceutical Technology Co., Ltd.

  公开号：EP4342463A1

  公开（公告）日：2024-03-27

  Provided is the use of stilbene compounds in the preparation of anti-tumor medicaments, and related is the pharmaceutical field. The stilbene compounds of the present invention are compounds represented by formula I, or salts thereof, or stereoisomers thereof, or solvates thereof. In the present invention, it is discovered that stilbene compounds have a dual effect of enriching T lymphocytes CD8+ in solid tumors and targeting the destruction of the inner wall of tumor blood vessels. While killing tumor cells by cytotoxic T lymphocyte antigen CD8+, the stilbenes cut off the blood supply to tumor tissues, cause rapid necrosis in solid tumors, greatly improve the killing effects on tumors, and inhibit tumor metastasis. Thereby, they can be used to prepare anti-tumor medicaments, and also used in combination with tumor immunotherapeutics to achieve synergistic anti-tumor effects. In addition, the stilbene compounds of the present invention can inhibit the growth of ocular surface blood vessels and be used in the preparation of medicaments for treating various eye diseases. The stilbene compounds of the present invention have good application prospects.

  提供的一种用途是茋类化合物在制备抗肿瘤药物中的应用，及其相关的药代动力学领域。本发明的茋类化合物是由式(I)所表示的化合物，或者其盐，或者其立体异构体，或者其溶剂化合物。在本发明中发现芪类化合物对于固体瘤内具有双重作用，一方面使得T淋巴细胞CD8+在实体瘤内富集，另一方面对于肿瘤血管内皮具有靶向性的破坏作用。芪类化合物在通过细胞毒性T淋巴细胞抗原CD8+杀死肿瘤细胞的同时，切断肿瘤组织的血液供应，使实体瘤快速坏死，大大提高了对肿瘤的杀伤效果，抑制肿瘤转移，从而可以制备成抗肿瘤药物，也可以与肿瘤免疫治疗药物联合使用达到协同抗肿瘤的效果。此外，本发明的芪类化合物还可以抑制眼表血管增生，具有制备治疗各类眼科疾病的药物的用途。本发明的芪类化合物具有良好的应用前景。
• Synthesis and biological evaluation of 4β-acrylamidopodophyllotoxin congeners as DNA damaging agents
  作者：Ahmed Kamal、Paidakula Suresh、M. Janaki Ramaiah、Adla Mallareddy、Banala Ashwini Kumar、Paidakula Raju、J. Vinay Gopal、S.N.C.V.L. Pushpavalli、A. Lavanya、Pranjal Sarma、Manika Pal-Bhadra

  DOI：10.1016/j.bmc.2011.06.017

  日期：2011.8

  A series of new 4 beta-acrylamidopodophyllotoxin derivatives (13a-o) were synthesized by coupling of substituted acrylic acids (10a-l and 11m-o) to the 4 beta-aminopodophyllotoxin. The synthesized derivatives 13a-o were evaluated for their cytotoxicity against five human cancer cell lines (breast, oral, colon, lung and ovarian). These podophyllotoxin conjugates have shown promising activity with GI(50) values ranging from <0.1 to 0.29 mu lM. Some of the compounds 13j, 13k and 13l that showed significant antiproliferative activity were also evaluated for related cytotoxic effects in MCF-7 cells, and compared to etoposide. These compounds (13j, 13k and 13l) showed G2/M cell cycle arrest and the apoptotic event was found to be due to both the single-strand DNA breaks as observed by comet assay as well as double-strand breaks as observed by the large accumulation of gamma H2AX foci. (C) 2011 Elsevier Ltd. All rights reserved.