2-cyano-2-(3-benzyloxy-4-methoxyphenyl)vinylbenzene sulfonate | 373392-94-0

• 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: 2-cyano-2-(3-benzyloxy-4-methoxyphenyl)vinylbenzene sulfonate
• CAS: 373392-94-0
• 化学式: C₂₃H₁₉NO₅S
• 分子量: 421.474
• InChiKey: DLMCSUWOODMBAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  85.62
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-cyano-2-(3-benzyloxy-4-methoxyphenyl)vinylbenzene sulfonate 在 sodium methylate 、 4-氯吡啶盐酸盐 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 5.25h， 生成 methyl 4-(3-benzyloxy-4-methoxyphenyl)-3-(pyrrol-1-yl)-2-thiophene carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z
• 作为产物：
  描述：

  (3-苄氧基-4-甲氧基苯基)-乙腈 在 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-cyano-2-(3-benzyloxy-4-methoxyphenyl)vinylbenzene sulfonate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z

文献信息

• Synthesis, reactivity and biological evaluation of novel halogenated tripentones
  作者：Vittoria Perri、Christophe Rochais、Thierry Cresteil、Patrick Dallemagne、Sylvain Rault

  DOI：10.1016/j.bmc.2009.09.027

  日期：2009.11

  We describe herein the synthesis and the biological evaluation of a novel series of a potent anticancer agents: the tripentones. For the first time, a halogen atom was introduced in high yields on the pyrrole ring of the tricycle. This synthesis and the reactivity of the novel halogenated tripentones in metallo-catalysed cross-coupling reactions will be described in that article. Finally their influence

  我们在本文中描述了一系列新的有效抗癌药：曲坦酮的合成和生物学评估。首次在三环的吡咯环上高产率地引入了卤素原子。该文章将描述金属催化的交叉偶联反应中新型卤代三萜酮的合成和反应性。最后，将讨论它们对生物活性的影响。
• Hydrogenative desulphurization of thienopyrrolizinones: An easy and selective access to (Z)-phenethylidenepyrrolizinones with in vitro cytotoxic activity
  作者：Vittoria Perri、Christophe Rochais、Jana Sopkova-de Oliveira Santos、Rémi Legay、Thierry Cresteil、Patrick Dallemagne、Sylvain Rault

  DOI：10.1016/j.ejmech.2009.12.021

  日期：2010.3

  Attempts in view to dearomatize some previously reported tripentones with potent antineoplastic activities led in thiophene series to an unexpected hydrogenative desulphurization reaction. The resulting (Z)-phenethylidenepyrrolizinones were tested in vitro over human epidermoid carcinoma KB cell line. The results of this biological evaluation indicated that the tricyclic core of our model can be cleaved with a partial respect of the activity. (C) 2009 Published by Elsevier Masson SAS.