N-(3-trifluoromethylbenzyl)-2-[(3-phenyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamide | 1241016-97-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(3-trifluoromethylbenzyl)-2-[(3-phenyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamide
• 英文别名: 2-[(2-oxo-3-phenyl-[1,2,4]triazino[2,3-c]quinazolin-6-yl)sulfanyl]-N-[[3-(trifluoromethyl)phenyl]methyl]acetamide
• CAS: 1241016-97-6
• 化学式: C₂₆H₁₈F₃N₅O₂S
• 分子量: 521.522
• InChiKey: HDYOYHJECWMNPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-[(3-trifluoromethylphenyl)methyl]-chloroacetamide 、 potassium 2-oxo-3-phenyl-2H-[1,2,4]triazino[2,3-c]quinazoline-6-thiolate 以 异丙醇 为溶剂， 反应 1.5h， 以99.9%的产率得到N-(3-trifluoromethylbenzyl)-2-[(3-phenyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamide
  参考文献：
  名称：

  Novel N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides: synthesis, cytotoxicity, anticancer activity, COMPARE analysis and docking

  摘要：

  The series of novel N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides were obtained by aminolysis of activated acids 1a-1d and by alkylation of potassium salts 2a-2d by N -aryl-2-chloroacetamies. The structures of compounds were determined by IR, H-1, C-13 NMR, LC- and EI-MS analyses. The results of cytotoxicity evaluation by bioluminescence inhibition of bacterium Photobacterium leiognathi Sh1 showed that compounds reveal moderate cytotoxicity. Screening of anticancer activity in vitro yielded the most active compounds 3t, 4b, 4f, 4l and 4n in micromolar concentrations with the GI(50) level (logGI(50) is from -7.57 to -4.05 for different cell lines, and logGI(50) mean graph midpoint varied from -5.30 to -4.50). Moreover, compound 4b had a distinctive selectivity against renal cancer, 4f-colon cancer and melanoma and 4l-renal cancer. The highest sensitivity to compound 4b showed renal cancer cell lines A498 (logGI(50) = -7.57). SAR-analysis was discussed, COMPARE analysis and docking was studied.The novel synthesis methods of the N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides are proposed. Anticancer activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds are discussed. SAR-analysis was discussed, and COMPARE analysis and docking was studied.

  DOI：

  10.1007/s00044-012-0257-x

文献信息

• Novel N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides: synthesis, cytotoxicity, anticancer activity, COMPARE analysis and docking
  作者：Sergey I. Kovalenko、Inna S. Nosulenko、Alexey Yu. Voskoboynik、Galina G. Berest、Lyudmila N. Antipenko、Alexey N. Antipenko、Andrey M. Katsev

  DOI：10.1007/s00044-012-0257-x

  日期：2013.6

  The series of novel N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides were obtained by aminolysis of activated acids 1a-1d and by alkylation of potassium salts 2a-2d by N -aryl-2-chloroacetamies. The structures of compounds were determined by IR, H-1, C-13 NMR, LC- and EI-MS analyses. The results of cytotoxicity evaluation by bioluminescence inhibition of bacterium Photobacterium leiognathi Sh1 showed that compounds reveal moderate cytotoxicity. Screening of anticancer activity in vitro yielded the most active compounds 3t, 4b, 4f, 4l and 4n in micromolar concentrations with the GI(50) level (logGI(50) is from -7.57 to -4.05 for different cell lines, and logGI(50) mean graph midpoint varied from -5.30 to -4.50). Moreover, compound 4b had a distinctive selectivity against renal cancer, 4f-colon cancer and melanoma and 4l-renal cancer. The highest sensitivity to compound 4b showed renal cancer cell lines A498 (logGI(50) = -7.57). SAR-analysis was discussed, COMPARE analysis and docking was studied.The novel synthesis methods of the N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides are proposed. Anticancer activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds are discussed. SAR-analysis was discussed, and COMPARE analysis and docking was studied.