4-ethoxy-N-(3,4,5-trimethoxybenzylidene)aniline | 151221-93-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-ethoxy-N-(3,4,5-trimethoxybenzylidene)aniline
• 英文别名: (E)‐N‐(4‐ethoxyphenyl)‐1‐(3,4,5‐trimethoxyphenyl)methanimine
• CAS: 151221-93-1
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: WMJHLUPXBDYNAF-XDHOZWIPSA-N

物化性质

• 沸点：
  459.1±45.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.86
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  49.28
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-ethoxy-N-(3,4,5-trimethoxybenzylidene)aniline 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以81.9%的产率得到4-ethoxy-N-(3,4,5-trimethoxybenzyl)aniline
  参考文献：
  名称：

  Synthesis and evaluation of a series of benzylaniline hydrochlorides as potential cytotoxic and antimitotic agents acting by inhibition of tubulin polymerization

  摘要：

  Although certain substituted cis-stilbenes have displayed potent tubulin polymerization inhibitory activity and significant cytotoxicities in cancer cell cultures, these compounds have limited aqueous solubility and are therefore difficult to formulate for in vivo evaluation. A series of water-soluble N-(3,4,5-trimethoxybenzyl)aniline salts has therefore been synthesized in which the olefinic bridge of the stilbenes is replaced by an aminomethylene hydrochloride moiety. A relationship was found between the size of the substituent in the 4-position of the aniline ring and both antitubulin activity and cytotoxicity, such that the smaller the substituent, the greater the potency. The most promising of the newly synthesized compounds was 4-methyl-N-(3,4,5-trimethoxybenzyl)aniline hydrochloride, with an IC50 value of 3.5 muM for inhibition of tubulin polymerization and cytotoxicity for a wide variety of cancer cell lines. The cytotoxicities of the benzylaniline hydrochlorides correlated remarkably well with their antitubulin activities.

  DOI：

  10.1021/jm00071a012
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 、 对乙氧基苯胺 以 乙醇 为溶剂， 反应 4.0h， 以82%的产率得到4-ethoxy-N-(3,4,5-trimethoxybenzylidene)aniline
  参考文献：
  名称：

  具有抗有丝分裂活性的 3-氯氮杂环丁烷-2-酮类药物的合成和抗增殖评价：Combretastatin A-4 的杂环桥类似物

  摘要：

  以微管蛋白为靶点的抗有丝分裂药物是最广泛使用的化疗药物之一。然而，多重耐药性的发展限制了它们的临床活性。我们报道了一系列新型 3-氯-β-内酰胺和 3,3-二氯-β-内酰胺（2-氮杂环丁酮）的合成和生物学特性，它们在结构上与微管蛋白聚合抑制剂和血管靶向剂 Combretastatin A 相关-4。这些化合物被评估为潜在的微管蛋白聚合抑制剂及其对乳腺癌细胞的抗增殖作用。许多化合物在 MCF-7 乳腺癌细胞中显示出有效的活性，例如化合物10n (3-氯-4-(3-羟基-4-甲氧基-苯基)-1-(3,4,5-三甲氧基苯基)氮杂环丁烷-2-酮)和化合物11n (3,3-二氯-4-(3-羟基-4-甲氧基苯基)-1-(3,4,5-三甲氧基苯基)-氮杂环丁烷-2-酮)，IC 50值分别为 17 和 31 nM，并且显示出与 Combretastatin A-4 相当的细胞效应。化合物10n对非致瘤性 HEK-293T

  DOI：

  10.3390/ph14111119

文献信息

• US5430062A
  申请人：——

  公开号：US5430062A

  公开（公告）日：1995-07-04
• [EN] STILBENE DERIVATIVES AS ANTICANCER AGENTS<br/>[FR] DERIVES DE STILBENE UTILISES COMME AGENTS ANTICANCEREUX
  申请人：——

  公开号：WO1993023357A1

  公开（公告）日：1993-11-25

  [EN] The present invention relates to stilbene derivatives which possess utility as anti-cancer agents. The compounds can be used to treat cancers which are susceptible to treatment therewith, and can be utilized in a method of treating such cancers. Pharmaceutical compositions containing the compounds are disclosed. Three preferred compounds amont those disclosed are (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene, (Z)-1-(4-methylphenyl)-2-(3,4,5-trimethoxyphenyl)ethene, and 4-methyl-3',4',5'-trimethoxybenzylaniline hydrochloride.
  [FR] Dérivés de stilbène présentant une utilité comme agents anticancéreux. On peut utiliser lesdits composés afin de traiter des cancers susceptibles d'être traités avec ceux-ci, et dans un procédé de traitement desdits cancers. L'invention concerne également des compositions pharmaceutiques contenant lesdits composés. Les composés préférés parmi ceux décrits dans l'invention sont (Z)-1-(4-méthoxyphényl)-2-(3,4,5-triméthoxyphényl)éthène, (Z)-1-(4-méthylphényl)-2-(3,4,5-triméthoxyphényl)éthène, et l'hydrochlorate de 4-méthyl-3',4',5'-triméthoxybenzylaniline.
• Synthesis and Antiproliferative Evaluation of 3-Chloroazetidin-2-ones with Antimitotic Activity: Heterocyclic Bridged Analogues of Combretastatin A-4
  作者：Azizah M. Malebari、Shu Wang、Thomas F. Greene、Niamh M. O’Boyle、Darren Fayne、Mohemmed Faraz Khan、Seema M. Nathwani、Brendan Twamley、Thomas McCabe、Daniela M. Zisterer、Mary J. Meegan

  DOI：10.3390/ph14111119

  日期：——

  development of multidrug resistance has limited their clinical activity. We report the synthesis and biological properties of a series of novel 3-chloro-β-lactams and 3,3-dichloro-β-lactams (2-azetidinones) that are structurally related to the tubulin polymerisation inhibitor and vascular targeting agent, Combretastatin A-4. These compounds were evaluated as potential tubulin polymerisation inhibitors and for

  以微管蛋白为靶点的抗有丝分裂药物是最广泛使用的化疗药物之一。然而，多重耐药性的发展限制了它们的临床活性。我们报道了一系列新型 3-氯-β-内酰胺和 3,3-二氯-β-内酰胺（2-氮杂环丁酮）的合成和生物学特性，它们在结构上与微管蛋白聚合抑制剂和血管靶向剂 Combretastatin A 相关-4。这些化合物被评估为潜在的微管蛋白聚合抑制剂及其对乳腺癌细胞的抗增殖作用。许多化合物在 MCF-7 乳腺癌细胞中显示出有效的活性，例如化合物10n (3-氯-4-(3-羟基-4-甲氧基-苯基)-1-(3,4,5-三甲氧基苯基)氮杂环丁烷-2-酮)和化合物11n (3,3-二氯-4-(3-羟基-4-甲氧基苯基)-1-(3,4,5-三甲氧基苯基)-氮杂环丁烷-2-酮)，IC 50值分别为 17 和 31 nM，并且显示出与 Combretastatin A-4 相当的细胞效应。化合物10n对非致瘤性 HEK-293T
• Synthesis and evaluation of a series of benzylaniline hydrochlorides as potential cytotoxic and antimitotic agents acting by inhibition of tubulin polymerization
  作者：Mark Cushman、Hu Ming He、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00071a012

  日期：1993.9

  Although certain substituted cis-stilbenes have displayed potent tubulin polymerization inhibitory activity and significant cytotoxicities in cancer cell cultures, these compounds have limited aqueous solubility and are therefore difficult to formulate for in vivo evaluation. A series of water-soluble N-(3,4,5-trimethoxybenzyl)aniline salts has therefore been synthesized in which the olefinic bridge of the stilbenes is replaced by an aminomethylene hydrochloride moiety. A relationship was found between the size of the substituent in the 4-position of the aniline ring and both antitubulin activity and cytotoxicity, such that the smaller the substituent, the greater the potency. The most promising of the newly synthesized compounds was 4-methyl-N-(3,4,5-trimethoxybenzyl)aniline hydrochloride, with an IC50 value of 3.5 muM for inhibition of tubulin polymerization and cytotoxicity for a wide variety of cancer cell lines. The cytotoxicities of the benzylaniline hydrochlorides correlated remarkably well with their antitubulin activities.