(4-ethylpiperazin-1-yl)(4-(4-morpholino-6-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)methanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4-ethylpiperazin-1-yl)(4-(4-morpholino-6-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)methanone
• 英文别名: (4-ethylpiperazin-1-yl)-[4-[4-morpholin-4-yl-6-(3,4,5-trimethoxyanilino)-1,3,5-triazin-2-yl]-3,6-dihydro-2H-pyridin-1-yl]methanone
• 化学式: C₂₈H₄₀N₈O₅
• 分子量: 568.676
• InChiKey: NASYTYRJAQFBIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,4-二氯-6-吗啉基-1,3,5-三嗪 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 19.0h， 生成 (4-ethylpiperazin-1-yl)(4-(4-morpholino-6-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)methanone
  参考文献：
  名称：

  Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors

  摘要：

  A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, 8j showed potent activity against the cancer cell lines such as HeLa, HepG2, A549 and MCF-7 with IC50 12.3 +/- 0.8, 9.6 +/- 0.4, 10.5 +/- 1.0 and 11.7 +/- 0.5 mu M respectively. 8j was taken up for elaborate biological studies and the cells in the cell cycle were arrested in G2/M phase. In addition, 8j was examined for its effect on the micro tubule system with a tubulin polymerization assay, immunofluorescence. 8j showed remarkable inhibition of tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. The studies suggested that 8j has a good binding affinity of -7.949 towards nocodazole binding site of tubulin while nocodazole has -7.462. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.06.060

文献信息

• Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors
  作者：Suresh Narva、Surendar Chitti、Suresh Amaroju、Debanjan Bhattacharjee、Bala Bhaskara Rao、Nishant Jain、Mallika Alvala、Kondapalli Venkata Gowri Chandra Sekhar

  DOI：10.1016/j.bmcl.2017.06.060

  日期：2017.8

  A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, 8j showed potent activity against the cancer cell lines such as HeLa, HepG2, A549 and MCF-7 with IC50 12.3 +/- 0.8, 9.6 +/- 0.4, 10.5 +/- 1.0 and 11.7 +/- 0.5 mu M respectively. 8j was taken up for elaborate biological studies and the cells in the cell cycle were arrested in G2/M phase. In addition, 8j was examined for its effect on the micro tubule system with a tubulin polymerization assay, immunofluorescence. 8j showed remarkable inhibition of tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. The studies suggested that 8j has a good binding affinity of -7.949 towards nocodazole binding site of tubulin while nocodazole has -7.462. (C) 2017 Elsevier Ltd. All rights reserved.