2-[[5-[3-(2-dimethylaminoethylsulfanyl)-1,2,4-triazin-5-yl]-1,2,4-triazin-3-yl]sulfanyl]-N,N-dimethyl-ethanamine | 1255789-71-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-[[5-[3-(2-dimethylaminoethylsulfanyl)-1,2,4-triazin-5-yl]-1,2,4-triazin-3-yl]sulfanyl]-N,N-dimethyl-ethanamine
• 英文别名: 2-[[5-[3-[2-(dimethylamino)ethylsulfanyl]-1,2,4-triazin-5-yl]-1,2,4-triazin-3-yl]sulfanyl]-N,N-dimethylethanamine
• CAS: 1255789-71-9
• 化学式: C₁₄H₂₂N₈S₂
• 分子量: 366.514
• InChiKey: FXVQGYNMHHGHLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-[(1,2,4-triazin-3-yl)thio]-N,N-dimethylethan-1-amine 在 potassium cyanide 作用下， 以 水 为溶剂， 以87%的产率得到2-[[5-[3-(2-dimethylaminoethylsulfanyl)-1,2,4-triazin-5-yl]-1,2,4-triazin-3-yl]sulfanyl]-N,N-dimethyl-ethanamine
  参考文献：
  名称：

  3-Alkylthio-1,2,4-triazine dimers with potent antimalarial activity

  摘要：

  We report on the discovery of 3-alkylthio-1,2,4-triazine dimers that are potently toxic to Plasmodium falciparum, with single digit nanomolar activity, and up to several thousand-fold lower toxicity to mammalian cells. They are equipotent against chloroquine-resistant strains of P. falciparum. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.065

文献信息

• Discovery of Potent and Fast-Acting Antimalarial Bis-1,2,4-triazines
  作者：Daniel L. Priebbenow、Mitch Mathiew、Da-Hua Shi、Jitendra R. Harjani、Julia G. Beveridge、Marina Chavchich、Michael D. Edstein、Sandra Duffy、Vicky M. Avery、Robert T. Jacobs、Stephen Brand、David M. Shackleford、Wen Wang、Longjin Zhong、Given Lee、Erin Tay、Helena Barker、Elly Crighton、Karen L. White、Susan A. Charman、Amanda De Paoli、Darren J. Creek、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.1c00044

  日期：2021.4.8

  potent in vitro activity against Plasmodium falciparum parasites were recently discovered. To improve the pharmacokinetic properties of the triazine derivatives, a new structure–activity relationship (SAR) investigation was initiated with a focus on enhancing the metabolic stability of lead compounds. These efforts led to the identification of second-generation highly potent antimalarial bis-triazines

  最近发现了新型 3,3'-二取代-5,5'-双（1,2,4-三嗪）化合物，具有有效的体外抗恶性疟原虫寄生虫的活性。为了改善三嗪衍生物的药代动力学特性，启动了一项新的构效关系（SAR）研究，重点是增强先导化合物的代谢稳定性。这些努力导致了第二代高效抗疟药双三嗪的鉴定，以三嗪23为例，其体外代谢稳定性显着改善（人和小鼠肝微粒体中的蛋白质为 8 和 42 μL/min/mg）。在 Peters 4 天试验中，还观察到二取代三嗪二聚体23可以抑制寄生虫血症，平均 ED 50值为 1.85 mg/kg/天，并表现出快速杀灭特性，揭示了一类新型口服抗疟化合物兴趣。
• 3-Alkylthio-1,2,4-triazine dimers with potent antimalarial activity
  作者：Kung Ban、Sandra Duffy、Yelena Khakham、Vicky M. Avery、Andrew Hughes、Oliver Montagnat、Kasiram Katneni、Eileen Ryan、Jonathan B. Baell

  DOI：10.1016/j.bmcl.2010.08.065

  日期：2010.10

  We report on the discovery of 3-alkylthio-1,2,4-triazine dimers that are potently toxic to Plasmodium falciparum, with single digit nanomolar activity, and up to several thousand-fold lower toxicity to mammalian cells. They are equipotent against chloroquine-resistant strains of P. falciparum. (c) 2010 Elsevier Ltd. All rights reserved.