methyl 1-hydroxy-4-(4-methoxyphenyl)-7,9-dimethylpyridazino[4,5-b]indolizine-10-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: methyl 1-hydroxy-4-(4-methoxyphenyl)-7,9-dimethylpyridazino[4,5-b]indolizine-10-carboxylate
• 英文别名: methyl 4-(4-methoxyphenyl)-7,9-dimethyl-1-oxo-2H-pyridazino[4,5-b]indolizine-10-carboxylate
• 化学式: C₂₁H₁₉N₃O₄
• 分子量: 377.4
• InChiKey: JOFMSYIIIDMHPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二甲基吡啶 在 一水合肼 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 、 乙腈 为溶剂， 反应 28.0h， 生成 methyl 1-hydroxy-4-(4-methoxyphenyl)-7,9-dimethylpyridazino[4,5-b]indolizine-10-carboxylate
  参考文献：
  名称：

  Studies on indolizines. Evaluation of their biological properties as microtubule-interacting agents and as melanoma targeting compounds

  摘要：

  With the aim of investigating new analogues of phenstatin with an indolizin-3-yl unit, in particular as the B-ring, three new series of compounds (6-8, 9-34 and 54) were synthesized and tested for interactions with tubulin polymerization and evaluated for cytotoxicity on an NCI-60 human cancer cell lines panel. The replacement of the 3'-hydroxy-4'-methoxyphenyl B-ring of phenstatin with substituted indolizine unit results in the conservation of both antitubulin and cytotoxic effect. Indolizines 9 and 17 were the most effective in the present study and showed the highest antiproliferative effect on melanoma cell lines MDA-MB-435 (GI(50) = 30 nM) and could serve as new lead compounds for the development of anti-cancer therapeutics. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.041

文献信息

• Studies on indolizines. Evaluation of their biological properties as microtubule-interacting agents and as melanoma targeting compounds
  作者：Alina Ghinet、Cristina-Maria Abuhaie、Philippe Gautret、Benoît Rigo、Joëlle Dubois、Amaury Farce、Dalila Belei、Elena Bîcu

  DOI：10.1016/j.ejmech.2014.10.041

  日期：2015.1

  With the aim of investigating new analogues of phenstatin with an indolizin-3-yl unit, in particular as the B-ring, three new series of compounds (6-8, 9-34 and 54) were synthesized and tested for interactions with tubulin polymerization and evaluated for cytotoxicity on an NCI-60 human cancer cell lines panel. The replacement of the 3'-hydroxy-4'-methoxyphenyl B-ring of phenstatin with substituted indolizine unit results in the conservation of both antitubulin and cytotoxic effect. Indolizines 9 and 17 were the most effective in the present study and showed the highest antiproliferative effect on melanoma cell lines MDA-MB-435 (GI(50) = 30 nM) and could serve as new lead compounds for the development of anti-cancer therapeutics. (C) 2014 Elsevier Masson SAS. All rights reserved.