3-benzyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide | 3866-81-7

• 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: 3-benzyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide
• 英文别名: 3-Benzyl-2,1,3-benzothiadiazin-4(1H)-one 2,2-dioxide；3-benzyl-2,2-dioxo-1H-2λ6,1,3-benzothiadiazin-4-one
• CAS: 3866-81-7
• 化学式: C₁₄H₁₂N₂O₃S
• 分子量: 288.327
• InChiKey: KJGZYYOOLJUWKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-benzyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide 在 三氟化硼乙醚 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 2.0h， 生成 3-Benzyl-1-(2-hydroxy-ethoxymethyl)-2,2-dioxo-2,3-dihydro-1H-2λ⁶-benzo[1,2,6]thiadiazin-4-one
  参考文献：
  名称：

  Benzothiadiazine dioxide acyclonucleosides as lead compounds for the development of new agents against human cytomegalovirus and varicella-zoster virus infections

  摘要：

  The first acyclonucleosides derived from 2,1,3-benzothiadiazine dioxides were synthesized. From their antiviral activity evaluation results these compounds might be considered as new leads in the search for inhibitors of human cytomegalovirus (CMV) and varicella-zoster virus (VZV) infections. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00149-2
• 作为产物：
  描述：

  benzylsulfamoyl chloride 在 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 3.0h， 生成 3-benzyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide
  参考文献：
  名称：

  新型苯并噻二嗪二氧化物衍生物的合成及抗病毒活性

  摘要：

  通过Mitsunobu反应通过烷基化合成了一系列2,1,3-和1,2,4-苯并噻二嗪衍生物，并评估了它们对ADV，HHV-6，Cox-B5和H-CMV的抗病毒活性。它们中的大多数在微摩尔水平上对一种或多种病毒株具有活性。除一种化合物具有更高的细胞毒性（最大无毒浓度为6μM）外，所有研究的分子均具有较弱的细胞毒性（最大无毒浓度>25μM）。

  DOI：

  10.1002/jhet.5570410516

文献信息

• Benzothiadiazine Dioxide Dibenzyl Derivatives as Potent Human Cytomegalovirus Inhibitors:  Synthesis and Comparative Molecular Field Analysis
  作者：Ana Martinez、Carmen Gil、Maria I. Abasolo、Ana Castro、Ana M. Bruno、Concepción Perez、Columbiana Prieto、Joaquín Otero

  DOI：10.1021/jm000033p

  日期：2000.8.1

  The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-donating, electron-withdrawing) in the phenyl ring of the benzyl moieties. The antiviral

  苯并噻二嗪二氧化物（BTD）衍生物是有效的非核苷人巨细胞病毒（HCMV）抑制剂。作为我们对这些化合物的全面结构-活性关系研究的一部分，我们现在合成了在苯基中具有不同对位取代基（烷基，苯基，给电子性，吸电子性）的N，N-和N，O-二苄基衍生物苄基部分的环。还通过实验测量了对HCMV（AD-169株）的抗病毒活性，显示出IC（50）值介于2.5和50 microM之间。比较分子场分析（CoMFA）用于基于32种不同的BTD衍生物生成模型，以描述对于增强针对HCMV的活性至关重要的结构和静电特征。与主要受体的空间（范德华）相互作用描述了抑制剂之间抗病毒活性的变化。最后，使用CoMFA模型设计了两组新型BTD衍生物。这些化合物的合成及随后的抗HCMV评估使我们能够维持这种新型HCMV抑制剂的活性。
• Synthesis of pseudonucleosides containing chiral sulfahydantoins as aglycone (II)
  作者：Georges Dewynter、Nourreddine Aouf、Zine Regainia、Jean-Louis Montero

  DOI：10.1016/0040-4020(95)00932-9

  日期：1996.1

  A series of chiral sulfahydantoins have been synthesized by alkaline cyclization starting from N-sulfamylaminoacid methyl esters. Regioselective glycosylation of these pseudopyrimidic heterocycles was carried out with a benzyl protecting group on the N-sulfonylcarbamic position. Best glycosylation results were obtained by preliminary silylation of sulfahydantoins, and their condensation with a tetraacylribofuranose

  从N-氨磺酰基氨基酸甲基酯开始，通过碱环化合成了一系列手性磺基缩乙胆苷。这些伪嘧啶杂环的区域选择性糖基化是在N-磺酰基氨基甲酸酯位置上的苄基保护基进行的。最佳的糖基化结果是通过对磺胺丁丹酮进行初步的甲硅烷基化，以及它们与四酰基核呋喃糖的缩合反应而获得的，从而产生呈β-异头构型的假核苷。
• Synthesis, biological evaluation and molecular modelling studies on benzothiadiazine derivatives as PDE4 selective inhibitors
  作者：Annalisa Tait、Amedeo Luppi、Armin Hatzelmann、Paola Fossa、Luisa Mosti

  DOI：10.1016/j.bmc.2004.10.055

  日期：2005.2

  A series of 2,1,3- and 1,2,4-benzothiadiazine derivatives (BTDs) were synthesized and evaluated for their inhibitory activity versus enzymatic isoforms PDE3, PDE4 and PDE7. The compounds characterized by the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at NI position of 2,1,3-benzothiadiazine core (8, 13, 18), were found active and selective at micromolar level versus PDE4 and could be studied as new leads for the treatment of asthma and COPD (Chronic Obstructive Pulmonary Disease). The antioxidant activity evaluation on the same compounds highlighted 13 as the most significative. Molecular modelling studies gave further support to biological results and suggested targeted modifications so as to improve their potency. (C)2004 Elsevier Ltd. All rights reserved.
• 2,1,3-Benzothiadiazine derivatives: synthesis and screening versus PDE4 enzyme
  作者：Annalisa Tait、Amedeo Luppi、Rossella Avallone、Mario Baraldi

  DOI：10.1016/j.farmac.2005.05.009

  日期：2005.8

  A series of N-1,3 disubstituted 2,1,3-benzothiadiazine derivatives (BTDs) were synthesized and evaluated for their inhibitory activity versus enzymatic isoform PDE4 extracted from U937 cell line. Some of the tested compounds showed a high PDE4 inhibitory activity at 100 microM and the IC(50) value of the most interesting terms were evaluated. The structure-activity relationships of these compounds showed that the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at N-1 position is important to obtain activity at micromolar level as previously reported. For the same compounds the antioxidant activity were evaluated highlighting 14 as the most significative one. The introduction of other bulky substituents in N-1 position is detrimental.
• Benzothiadiazine dioxides (BTD) derivatives as non-nucleoside human cytomegalovirus (HCMV) inhibitors. study of structural requirements for biological activity☆
  作者：Ana Martinez、Carmen Gil、Ana Castro、Concepción Pérez、Columbiana Prieto、Joaquin Otero

  DOI：10.1016/s0968-0896(03)00148-2

  日期：2003.5.29

  Two new series of BTD derivatives have been synthesised allowing to explore the steric requirements for their biological activity. The N3-alkylBTD compounds have shown antiviral activity in the same order or lower than previously prepared compounds. However, the cytotoxicity values observed prevent this new series of BTD derivatives from its potential therapeutic application. Concerning BTD derivatives with the modified linker attached to N1 position, we have obtained new non-nucleoside anti-HCMV derivatives. The activity against HCMV is shown at concentrations that were 10-fold lower than the concentration that was toxic for the host cells, which confirm that these derivatives show a specific antiviral effect against HCMV. SAR conclusions derived from these last compounds have provided new knowledge about the structural requirements of BTD showing certain positions that could be modified for enhancing the anti-HCMV action. (C) 2003 Elsevier Science Ltd. All rights reserved.