N₂-benzyl-N₄-cyanomethyl-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N₂-benzyl-N₄-cyanomethyl-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine
• 英文别名: 2-(2-Benzyl-1,1,3-trioxo-pyrrolo[1,2-b][1,2,4,6]thiatriazin-4-yl)acetonitrile；2-(2-benzyl-1,1,3-trioxopyrrolo[1,2-b][1,2,4,6]thiatriazin-4-yl)acetonitrile
• 化学式: C₁₄H₁₂N₄O₃S
• 分子量: 316.34
• InChiKey: DLBBLGITJVDHRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  94.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 叠氮磷酸二苯酯 、 水 、 sodium hydride 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 36.25h， 生成 N₂-benzyl-N₄-cyanomethyl-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of N2,N4-disubstituted-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine derivatives as HIV-1 NNRTIs

  摘要：

  A series of N-2,N-4-disubstituted-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine derivatives (PTTDs) was designed and synthesized by a facile route. The biological assay results showed that five most potent compounds displayed inhibitory activity against HIV-1 at low micromolar concentrations (EC50 = 5.1-8.9 mu M). Structure-activity relationship analysis indicated that N-2-(3-halogenated-benzyl) analogues were more potent than N-2-(unsubstituted-benzyl) analogues. The N-4-substitutions contributed to the antiviral activity in the following order: 2-/3-cyano substituted benzyl > 2-/3-halogenated benzyl > non-substituted benzyl > 4-halogenated benzyl. Docking studies of the representative compound revealed the binding conformation of these compounds and provided critical insights for the further development of PTTD analogues. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.009

文献信息

• Design, synthesis and biological evaluation of N2,N4-disubstituted-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine derivatives as HIV-1 NNRTIs
  作者：Wenmin Chen、Peng Zhan、Erik De Clercq、Christophe Pannecouque、Jan Balzarini、Xin Jiang、Xinyong Liu

  DOI：10.1016/j.bmc.2013.09.009

  日期：2013.11

  A series of N-2,N-4-disubstituted-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine derivatives (PTTDs) was designed and synthesized by a facile route. The biological assay results showed that five most potent compounds displayed inhibitory activity against HIV-1 at low micromolar concentrations (EC50 = 5.1-8.9 mu M). Structure-activity relationship analysis indicated that N-2-(3-halogenated-benzyl) analogues were more potent than N-2-(unsubstituted-benzyl) analogues. The N-4-substitutions contributed to the antiviral activity in the following order: 2-/3-cyano substituted benzyl > 2-/3-halogenated benzyl > non-substituted benzyl > 4-halogenated benzyl. Docking studies of the representative compound revealed the binding conformation of these compounds and provided critical insights for the further development of PTTD analogues. (C) 2013 Elsevier Ltd. All rights reserved.