Z-(9-ethyl-9H-carbazol-3-yl) (3,4,5-trimethoxyphenyl)methanone oxime

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Z-(9-ethyl-9H-carbazol-3-yl) (3,4,5-trimethoxyphenyl)methanone oxime
• 英文别名: (NZ)-N-[(9-ethylcarbazol-3-yl)-(3,4,5-trimethoxyphenyl)methylidene]hydroxylamine
• 化学式: C₂₄H₂₄N₂O₄
• 分子量: 404.466
• InChiKey: AOYAFSOBIXALGQ-BZZOAKBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  65.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-溴-3,4,5-三甲氧基苯 在 吡啶 、 重铬酸吡啶 、 正丁基锂 、 盐酸羟胺 、 四丁基硫酸氢铵 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 E-(9-ethyl-9H-carbazol-3-yl) (3,4,5-trimethoxyphenyl)methanone oxime 、 Z-(9-ethyl-9H-carbazol-3-yl) (3,4,5-trimethoxyphenyl)methanone oxime
  参考文献：
  名称：

  Exploring the size adaptability of the B ring binding zone of the colchicine site of tubulin with para-nitrogen substituted isocombretastatins

  摘要：

  We have synthesized and assayed dimethylaminophenyl, pyrrolidin-1-ylphenyl and carbazole containing phenstatins and isocombretastatins as analogues of the highly potent indoleisocombretastatins with extended or reduced ring sizes. This is an attempt to explore beyond the structural constraints of the X-ray crystal structures the zone of the colchicine site where the tropolone ring of colchicine binds to tubulin (zone 1). The isocombretastatins display up to 30 fold increased water solubility when compared with combretastatin A-4, potent inhibition of tubulin polymerization, and nanomolar cytotoxicities against several human cancer cell lines irrespective of the size of the B ring. On the other hand, substitutions ortho to the nitrogen cause an important reduction in potency. We have also shown that representative compounds inhibit autophagy. These results show that zone 1 can adapt to systems of different size as far as they stay in a common plane, but does not tolerate substituents protruding above or below it. These results can help in the understanding of the binding modes of structures with similar systems and in the design of new colchicine site ligands. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.047

文献信息

• Exploring the size adaptability of the B ring binding zone of the colchicine site of tubulin with para-nitrogen substituted isocombretastatins
  作者：Carmen Jiménez、Younes Ellahioui、Raquel Álvarez、Laura Aramburu、Alejandra Riesco、Myriam González、Alba Vicente、Abdelaziz Dahdouh、Ahmed Ibn Mansour、Carlos Jiménez、Diego Martín、Rogelio G. Sarmiento、Manuel Medarde、Esther Caballero、Rafael Peláez

  DOI：10.1016/j.ejmech.2015.05.047

  日期：2015.7

  We have synthesized and assayed dimethylaminophenyl, pyrrolidin-1-ylphenyl and carbazole containing phenstatins and isocombretastatins as analogues of the highly potent indoleisocombretastatins with extended or reduced ring sizes. This is an attempt to explore beyond the structural constraints of the X-ray crystal structures the zone of the colchicine site where the tropolone ring of colchicine binds to tubulin (zone 1). The isocombretastatins display up to 30 fold increased water solubility when compared with combretastatin A-4, potent inhibition of tubulin polymerization, and nanomolar cytotoxicities against several human cancer cell lines irrespective of the size of the B ring. On the other hand, substitutions ortho to the nitrogen cause an important reduction in potency. We have also shown that representative compounds inhibit autophagy. These results show that zone 1 can adapt to systems of different size as far as they stay in a common plane, but does not tolerate substituents protruding above or below it. These results can help in the understanding of the binding modes of structures with similar systems and in the design of new colchicine site ligands. (C) 2015 Elsevier Masson SAS. All rights reserved.