5-(((1-((5-methyl-2-thiomorpholinopyridin-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)-3-(3,4,5-trimethoxyphenyl)isoxazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(((1-((5-methyl-2-thiomorpholinopyridin-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)-3-(3,4,5-trimethoxyphenyl)isoxazole
• 英文别名: 5-[[1-[(5-Methyl-2-thiomorpholin-4-ylpyridin-3-yl)methyl]triazol-4-yl]methoxymethyl]-3-(3,4,5-trimethoxyphenyl)-1,2-oxazole；5-[[1-[(5-methyl-2-thiomorpholin-4-ylpyridin-3-yl)methyl]triazol-4-yl]methoxymethyl]-3-(3,4,5-trimethoxyphenyl)-1,2-oxazole
• 化学式: C₂₇H₃₂N₆O₅S
• 分子量: 552.654
• InChiKey: BOEPBZOUMNMGOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛肟 在 吡啶 、 N-氯代丁二酰亚胺 、 copper(ll) sulfate pentahydrate 、 sodium hydride 、 sodium ascorbate 作用下， 以 四氢呋喃 、 氯仿 、 水 、 叔丁醇 为溶剂， 反应 21.5h， 生成 5-(((1-((5-methyl-2-thiomorpholinopyridin-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)-3-(3,4,5-trimethoxyphenyl)isoxazole
  参考文献：
  名称：

  Synthesis and structure–activity relationships of pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles as potent inhibitors of tubulin polymerization

  摘要：

  Three series of compounds; pyridinyl-1H-1,2,3-triazoles, pyridinyl-1H-1,2,3-triazolylisoxazoles and pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles with TMP moiety were designed, synthesized and screened for their anti-cancer and anti-tubulin properties. By sequentially designing three series of compounds comprising of dihydroisoxazole in the linker, a small substituent like chlorine on one side (R-1) and aromatic group (R) on the pyridine ring, we have optimized the anti-cancer as well as anti-tubulin activity. Pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles 28b and 28c were found to be potent anti-cancer agents against all the cell lines tested with a concomitant accumulation of cells in the G2/M phase of the cell cycle. Molecular modeling suggests that the trimethoxyphenyl ring in 28b and 28c occupies the cholchicine binding domain of beta-tubulin, whereas, the dihydroisoxazole extends towards the interface of alpha,beta-tubulin. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.063

文献信息

• Synthesis and structure–activity relationships of pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles as potent inhibitors of tubulin polymerization
  作者：P. Suman、T. Ramalinga Murthy、K. Rajkumar、D. Srikanth、Ch. Dayakar、Chandan Kishor、Anthony Addlagatta、Shasi V. Kalivendi、B. China Raju

  DOI：10.1016/j.ejmech.2014.11.063

  日期：2015.1

  Three series of compounds; pyridinyl-1H-1,2,3-triazoles, pyridinyl-1H-1,2,3-triazolylisoxazoles and pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles with TMP moiety were designed, synthesized and screened for their anti-cancer and anti-tubulin properties. By sequentially designing three series of compounds comprising of dihydroisoxazole in the linker, a small substituent like chlorine on one side (R-1) and aromatic group (R) on the pyridine ring, we have optimized the anti-cancer as well as anti-tubulin activity. Pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles 28b and 28c were found to be potent anti-cancer agents against all the cell lines tested with a concomitant accumulation of cells in the G2/M phase of the cell cycle. Molecular modeling suggests that the trimethoxyphenyl ring in 28b and 28c occupies the cholchicine binding domain of beta-tubulin, whereas, the dihydroisoxazole extends towards the interface of alpha,beta-tubulin. (C) 2014 Elsevier Masson SAS. All rights reserved.