N₂-benzyl-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-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine
• 英文别名: 2-benzyl-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine；2-benzyl-1,1-dioxo-4H-pyrrolo[1,2-b][1,2,4,6]thiatriazin-3-one
• 化学式: C₁₂H₁₁N₃O₃S
• 分子量: 277.304
• InChiKey: PLWLKHPGDXLYBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N₂-benzyl-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine 、 3-氯丙烯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.25h， 以65%的产率得到N₂-benzyl N₄-allyl-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
• 作为产物：
  描述：

  benzylsulfamoyl chloride 在 叠氮磷酸二苯酯 、 sodium hydride 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 甲苯 、 mineral oil 为溶剂， 反应 54.0h， 生成 N₂-benzyl-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine
  参考文献：
  名称：

  1,1,3-Trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine 衍生物的简易合成：一种新的杂环系统

  摘要：

  我们报道了一种合成吡咯并 [1,2-b][1,2,4,6] 噻三嗪 (PTTD) 衍生物的简便有效的方法：一种新的桥头氮杂环系统。用N-苄基氨磺酰氯处理吡咯-2-羧酸甲酯，然后进行水解反应，得到1-苄基氨磺酰基-1H-吡咯-2-羧酸，通过Curtius重排用二苯基磷酸酯处理进行闭环反应；随后的烷基化反应提供了所需的 2,4-二取代-1,1,3-三氧代-2H,4H-PTTD。

  DOI：

  10.1002/hc.21123

文献信息

• Facile Synthesis of Derivatives of 1,1,3-Trioxo-2<i>H</i>,4<i>H</i>-pyrrolo[1,2-<i>b</i>][1,2,4,6]thiatriazine: A New Heterocyclic System
  作者：Wenmin Chen、Peng Zhan、Diwakar Rai、Boshi Huang、Jiapei Yang、Xinyong Liu

  DOI：10.1002/hc.21123

  日期：2013.11

  We reported a facile and efficient methodology to synthesize derivatives of pyrrolo[1,2-b][1,2,4,6]thiatriazine (PTTD): a new bridgehead nitrogen heterocyclic system. Treatment of methyl pyrrole-2-carboxylate with N-benzylsulfamoyl chlorides followed by subsequent hydrolysis reaction afforded 1-benzylsulfamoyl-1H-pyrrole-2-carboxylic acids, which underwent ring-closing reaction by treatment with diphenyl

  我们报道了一种合成吡咯并 [1,2-b][1,2,4,6] 噻三嗪 (PTTD) 衍生物的简便有效的方法：一种新的桥头氮杂环系统。用N-苄基氨磺酰氯处理吡咯-2-羧酸甲酯，然后进行水解反应，得到1-苄基氨磺酰基-1H-吡咯-2-羧酸，通过Curtius重排用二苯基磷酸酯处理进行闭环反应；随后的烷基化反应提供了所需的 2,4-二取代-1,1,3-三氧代-2H,4H-PTTD。
• 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.