3-benzyl-6,7-dimethoxy-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide | 847997-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-benzyl-6,7-dimethoxy-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide
• CAS: 847997-70-0
• 化学式: C₁₆H₁₆N₂O₅S
• 分子量: 348.379
• InChiKey: ZTRXDSSTRWPJSE-UHFFFAOYSA-N

物化性质

• 熔点：
  160-161 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  547.0±60.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84.94
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-benzyl-6,7-dimethoxy-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide 、 3,5-二叔丁基-4-羟基苄醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以57%的产率得到
  参考文献：
  名称：

  2,1,3-Benzothiadiazine derivatives: synthesis and screening versus PDE4 enzyme

  摘要：

  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.

  DOI：

  10.1016/j.farmac.2005.05.009
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸甲酯 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-6,7-dimethoxy-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide
  参考文献：
  名称：

  2,1,3-Benzothiadiazine derivatives: synthesis and screening versus PDE4 enzyme

  摘要：

  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.

  DOI：

  10.1016/j.farmac.2005.05.009

文献信息

• 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.