2-(3-fluorophenyl)-5-(4-acetyl-1-piperazinyl)-4-(3,4,5-trimethoxybenzoyl)-1,2,3-triazole

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(3-fluorophenyl)-5-(4-acetyl-1-piperazinyl)-4-(3,4,5-trimethoxybenzoyl)-1,2,3-triazole
• 英文别名: 2-(3-fluorophenyl)-5-(N-acetylpiperazin-1-yl)-4-(3,4,5-trimethoxybenzoyl)-2H-1,2,3-triazole；1-[4-[2-(3-Fluorophenyl)-5-(3,4,5-trimethoxybenzoyl)triazol-4-yl]piperazin-1-yl]ethanone；1-[4-[2-(3-fluorophenyl)-5-(3,4,5-trimethoxybenzoyl)triazol-4-yl]piperazin-1-yl]ethanone
• 化学式: C₂₄H₂₆FN₅O₅
• 分子量: 483.499
• InChiKey: CDAMWHYGOBVBFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酸甲酯 在 盐酸 、 copper diacetate 、 sodium hydride 、 sodium nitrite 作用下， 以 水 、 乙腈 、 mineral oil 为溶剂， 反应 9.83h， 生成 2-(3-fluorophenyl)-5-(4-acetyl-1-piperazinyl)-4-(3,4,5-trimethoxybenzoyl)-1,2,3-triazole
  参考文献：
  名称：

  Design, synthesis and bio-evaluation of novel 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazoles as the tubulin polymerization inhibitors

  摘要：

  A series of 2-aryl-4-(3,4,5-trimethoxybenzoyl)-5-substituted-1,2,3-triazoles were designed, synthesized and evaluated for the anticancer activities. Based on the model of DMAM-colchicine-tubulin complex interactions, various saturated nitrogen-containing heterocycles were introduced to the C5-position of 1,2,3-triazol to interact with a tolerant region at the entrance of the binding-pocket and increase the aqueous solubility of the compounds. All designed compounds were concisely synthesized by one-pot oxidative cyclization. Most compounds exhibited moderate antiproliferative activity with IC50 values in the micromolar to sub-micromolar range. Among them, 5g posed N-acyl-piperazine moiety at the C5-position of B-ring showed most potent against cancer cells, with IC50 values of 0.084-0.221 mu M 5g potently disrupted microtubule/tubulin dynamics, induced cell cycle arrest at G2/M phase in SGC-7901 cells. In addition, molecular modeling studies suggested that 5g probably binds to the colchicine site of tubulin. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111846

文献信息

• Design, synthesis and bio-evaluation of novel 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazoles as the tubulin polymerization inhibitors
  作者：Liancheng Huang、Meng Liu、Shuai Man、Deyi Ma、Dongjie Feng、Zhongqiao Sun、Qi Guan、Daiying Zuo、Yingliang Wu、Weige Zhang、Kai Bao

  DOI：10.1016/j.ejmech.2019.111846

  日期：2020.1

  A series of 2-aryl-4-(3,4,5-trimethoxybenzoyl)-5-substituted-1,2,3-triazoles were designed, synthesized and evaluated for the anticancer activities. Based on the model of DMAM-colchicine-tubulin complex interactions, various saturated nitrogen-containing heterocycles were introduced to the C5-position of 1,2,3-triazol to interact with a tolerant region at the entrance of the binding-pocket and increase the aqueous solubility of the compounds. All designed compounds were concisely synthesized by one-pot oxidative cyclization. Most compounds exhibited moderate antiproliferative activity with IC50 values in the micromolar to sub-micromolar range. Among them, 5g posed N-acyl-piperazine moiety at the C5-position of B-ring showed most potent against cancer cells, with IC50 values of 0.084-0.221 mu M 5g potently disrupted microtubule/tubulin dynamics, induced cell cycle arrest at G2/M phase in SGC-7901 cells. In addition, molecular modeling studies suggested that 5g probably binds to the colchicine site of tubulin. (C) 2019 Elsevier Masson SAS. All rights reserved.