9-ethyl-2-methoxy-6-(4-methylnaphthalene-1-carbonyl)-9H-carbazole

• 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: 9-ethyl-2-methoxy-6-(4-methylnaphthalene-1-carbonyl)-9H-carbazole
• 英文别名: (9-Ethyl-7-methoxycarbazol-3-yl)-(4-methylnaphthalen-1-yl)methanone；(9-ethyl-7-methoxycarbazol-3-yl)-(4-methylnaphthalen-1-yl)methanone
• 化学式: C₂₇H₂₃NO₂
• 分子量: 393.485
• InChiKey: FLOPIVXDSYCUEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-甲氧基咔唑 在 aluminum (III) chloride 、 caesium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 18.5h， 生成 9-ethyl-2-methoxy-6-(4-methylnaphthalene-1-carbonyl)-9H-carbazole
  参考文献：
  名称：

  Modified carbazoles destabilize microtubules and kill glioblastoma multiform cells

  摘要：

  Small molecules that target microtubules (MTs) represent promising therapeutics to treat certain types of cancer, including glioblastoma multiform (GBM). We synthesized modified carbazoles and evaluated their antitumor activity in GBM cells in culture. Modified carbazoles with an ethyl moiety linked to the nitrogen of the carbazole and a carbonyl moiety linked to distinct biaromatic rings exhibited remarkably different killing activities in human GBM cell lines and patient-derived GBM cells, with IC50 values from 67 to > 10,000 nM. Measures of the activity of modified carbazoles with tubulin and microtubules coupled to molecular docking studies show that these compounds bind to the colchicine site of tubulin in a unique low interaction space that inhibits tubulin assembly. The modified carbazoles reported here represent novel chemical tools to better understand how small molecules disrupt MT functions and kill devastating cancers such as GBM. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.026

文献信息

• MODIFIED CARBAZOLES AS THERAPEUTIC AGENTS
  申请人：UNIVERSITY OF WASHINGTON

  公开号：US20210094949A1

  公开（公告）日：2021-04-01

  This disclosure relates to compounds that target microtubules, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases. More particularly, this disclosure relates to modified carbazole compounds and pharmaceutical compositions thereof, methods of targeting microtubules with these compounds, and methods of treating diseases affected by microtubule disruption.