2-[2-(3,5-bis(trifluoromethyl)benzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid methyl ester | 1349171-04-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-[2-(3,5-bis(trifluoromethyl)benzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid methyl ester
• CAS: 1349171-04-5
• 化学式: C₂₀H₁₅F₆NO₄S
• 分子量: 479.4
• InChiKey: VKCZEEUJDBBAJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.49
• 重原子数：
  32.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.68
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-[2-(3,5-bis(trifluoromethyl)benzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid methyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 12.0h， 以93%的产率得到2-(2-(3,5-bis(trifluoromethyl)benzyl)-1,1-dioxido-3,4-dihydro-2H-1,2-benzothiazin-yl)acetic acid methyl ester
  参考文献：
  名称：

  1,2-Benzothiazine 1,1-dioxide carboxylate derivatives as novel potent inhibitors of aldose reductase

  摘要：

  Due to the importance of aldose reductase (ALR2) as a potential drug target in the treatment of diabetic complications, there are increasing interests in design and synthesis of ALR2 inhibitors. Here, we prepared 1,2-benzothiazine 1,1-dioxide acetic acid derivatives and investigated their inhibition activity. Most of these derivatives were found to be active with IC50 values ranging from 0.11 mu M to 10.42 mu M, and compound 8d, 2-[2-(4-bromo-2-fluorobenzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid, showed the most potent inhibition activity. Further, SAR and docking studies suggest that in comparison with the alpha,beta-unsaturated derivatives, the saturated carboxylic acid derivatives had a greater binding affinity with the enzyme and thus an enhanced inhibition activity. Therefore, development of more powerful ARIs based on benzothiazine 1,1-dioxide by stereo-controlled synthesis could be expected. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.07.051
• 作为产物：
  描述：

  4-羟基-2H-1,2-苯并噻嗪-3-羧酸甲酯1,1-二氧化物 在 盐酸 、 水 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲苯 、 乙腈 为溶剂， 反应 21.0h， 生成 2-[2-(3,5-bis(trifluoromethyl)benzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid methyl ester
  参考文献：
  名称：

  1,2-Benzothiazine 1,1-dioxide carboxylate derivatives as novel potent inhibitors of aldose reductase

  摘要：

  Due to the importance of aldose reductase (ALR2) as a potential drug target in the treatment of diabetic complications, there are increasing interests in design and synthesis of ALR2 inhibitors. Here, we prepared 1,2-benzothiazine 1,1-dioxide acetic acid derivatives and investigated their inhibition activity. Most of these derivatives were found to be active with IC50 values ranging from 0.11 mu M to 10.42 mu M, and compound 8d, 2-[2-(4-bromo-2-fluorobenzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid, showed the most potent inhibition activity. Further, SAR and docking studies suggest that in comparison with the alpha,beta-unsaturated derivatives, the saturated carboxylic acid derivatives had a greater binding affinity with the enzyme and thus an enhanced inhibition activity. Therefore, development of more powerful ARIs based on benzothiazine 1,1-dioxide by stereo-controlled synthesis could be expected. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.07.051