N-(2,4-dinitrophenyl)-N-deacetylcolchicine

• 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: N-(2,4-dinitrophenyl)-N-deacetylcolchicine
• 英文别名: (7S)-7-(2,4-dinitroanilino)-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one
• 化学式: C₂₆H₂₅N₃O₉
• 分子量: 523.499
• InChiKey: GIKMSLYWODVLMA-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  158
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (7S)-7-氨基-1,2,3,10-四甲氧基-6,7-二氢-5H-苯并[g]庚搭烯-9-酮 、 2,4-二硝基氟苯 以45%的产率得到N-(2,4-dinitrophenyl)-N-deacetylcolchicine
  参考文献：
  名称：

  Conformational analysis of colchicinoids containing an electron-deficient aromatic ring on the B ring

  摘要：

  A dinitrophenyl substituent at the C-7 position of N-deacetylcolchicine and N-deacetylisocolchicine was shown to perturb the H-1 NMR and circular dichroic spectra of colchicinoid ring systems. The perturbations were explained by an interaction between the C-7 substituent and the A and/or C rings. Other aromatic substituents or large substituents located at the C-7 position (J. Med. Chem. 1983, 26, 1365) have not been reported to influence the aS-aR equilibrium of the phenyltropone ring junction. It was concluded that the sterically unfavored atropisomers were stabilized by the interaction of an electron-deficient ring with the more electron-rich A ring of the colchicinoid molecules.

  DOI：

  10.1021/jo00062a016

文献信息

• Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs
  作者：Michael Cifuentes、Brett Schilling、Rudravajhala Ravindra、Jacquelyn Winter、Mark E. Janik

  DOI：10.1016/j.bmcl.2006.02.010

  日期：2006.5

  A series of modified colchicine and isocolchicine analogs (C-7 substituent) were synthesized and evaluated in vitro against a PC3 cancer cell line and for inhibition of microtubule polymerization. The colchicine analogs all displayed strong inhibition of tubulin polymerization, while compounds 6 and 20 also possessed an increased cytotoxic activity as compared to colchicine. More importantly, isocolchicine

  合成了一系列修饰的秋水仙碱和异秋水仙碱类似物（C-7取代基），并在体外针对PC3癌细胞系进行了评估，并评估了其对微管聚合的抑制作用。秋水仙碱类似物均显示出对微管蛋白聚合的强烈抑制，而化合物6和20与秋水仙碱相比也具有增加的细胞毒性活性。更重要的是，异秋水仙碱类似物7、15和17表现出微管聚合的抑制作用，IC（50）值为58至68μM。此外，7显示强大的细胞毒活性，IC（50）= 93nM，比秋水仙碱类似物12更有效。