2-(2,4,5-trifluorobenzyl)-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide | 1349170-98-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-(2,4,5-trifluorobenzyl)-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide
• 英文别名: 1,1-dioxo-2-[(2,4,5-trifluorophenyl)methyl]-3H-1lambda6,2-benzothiazin-4-one；1,1-dioxo-2-[(2,4,5-trifluorophenyl)methyl]-3H-1λ6,2-benzothiazin-4-one
• CAS: 1349170-98-4
• 化学式: C₁₅H₁₀F₃NO₃S
• 分子量: 341.311
• InChiKey: LJVCYWQNVIWFKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(2,4,5-trifluorobenzyl)-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide 在 盐酸 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 13.0h， 生成 endo-2-[2-(2,4,5-trifluorobenzyl)-1,1-dioxo-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid
  参考文献：
  名称：

  1,2-苯并噻嗪-1,1-二氧化物羧酸盐作为醛糖还原酶抑制剂的烯属异构体的选择性合成和比较活性†

  摘要：

  通过Wittig烯化反应在各种温度条件下选择性合成1,2-苯并噻嗪-1,1-二氧化物的α，β-和β，γ-不饱和羧酸酯异构体。在40°C时，会形成具有高Z立体选择性（83–87％）的α，β-不饱和酯，而在100–120°C（77–96％）时，会优先形成具有中等至优异区域选择性的β，γ-不饱和酯。 ）。发现酸异构体按活性β，γ-不饱和> Z -α，β-不饱和> E -α，β-不饱和异构体的顺序抑制醛糖还原酶。β，γ-不饱和异构体7b，2- [2-（4-溴-2-氟苄基）-1,1-二氧化物2 H -1,2-苯并噻嗪-4（3 H）-亚烷基]乙酸具有最强的抑制活性，IC 50值为0.057μM。对接研究进一步支持了这一点。

  DOI：

  10.1039/c4ra01016g
• 作为产物：
  描述：

  saccharin sodium salt 在 盐酸 、 甲醇 、 水 、 sodium 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 20.5h， 生成 2-(2,4,5-trifluorobenzyl)-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide
  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

文献信息

• Copper-Catalyzed Asymmetric Synthesis and Comparative Aldose Reductase Inhibition Activity of (+)/(−)-1,2-Benzothiazine-1,1-dioxide Acetic Acid Derivatives
  作者：Shagufta Parveen、Saghir Hussain、Xiangyu Qin、Xin Hao、Shaojuan Zhu、Miao Rui、Shuzhen Zhang、Fengyan Fu、Bing Ma、Qun Yu、Changjin Zhu

  DOI：10.1021/jo500338c

  日期：2014.6.6

  the α,β-unsaturated carboxylate class was developed by which synthesis of (+)- and (−)-enantiomers of 1,2-benzothiazine-1,1-dioxide acetates has been achieved with a good yield and an excellent level of enantioselectivity. A comparative structure–activity relationship study yielded the following order of aldose reductase inhibition activity: (−)-enantiomers > racemic > (+)-enantiomers. Further, a molecular

  开发了用于α，β-不饱和羧酸酯类不对称1,4-氢化硅烷化的铜催化剂体系，通过该体系合成1,2-苯并噻嗪-1,1-二氧化物乙酸酯的（+）-和（-）-对映异构体已经以良好的收率和优异的对映选择性水平实现了本发明。对比结构-活性关系研究得出了醛糖还原酶抑制活性的以下顺序：（-）-对映体>外消旋>（+）-对映体。此外，分子对接研究表明（-）-对映异构体具有显着的结合亲和力，因此抑制活性增强。
• Chiral resolution, determination of absolute configuration, and biological evaluation of (1,2-benzothiazin-4-yl)acetic acid enantiomers as aldose reductase inhibitors
  作者：Xin Hao、Xiangyu Qin、Saghir Hussain、Shagufta Parveen、Wei Zhang、Fengyan Fu、Bing Ma、Changjin Zhu

  DOI：10.3109/14756366.2014.961447

  日期：2015.9.3

  A novel series of (1,2-benzothiazin-4-yl)acetic acid enantiomers was prepared by chiral resolution, and their absolute configurations were determined using the PGME method. The biological evaluation of the racemate and single enantiomers has shown a remarkable difference for the aldose reductase inhibitory activity and selectivity. The (R)-(-)-enantiomer exhibited the strongest aldose reductase activity

  通过手性拆分制备了一系列新的（1,2-苯并噻嗪-4-基）乙酸对映体，并使用PGME方法确定了它们的绝对构型。外消旋体和单一对映体的生物学评估显示醛糖还原酶抑制活性和选择性存在显着差异。（R）-（-）-对映异构体表现出最强的醛糖还原酶活性，IC（50）值为0.120μM，是S-（+）-对映异构体的35倍。因此，显示该支架的C4位置的立体中心对活性和选择性具有重大影响。
• 1,2-Benzothiazine 1,1-dioxide carboxylate derivatives as novel potent inhibitors of aldose reductase
  作者：Xin Chen、Shuzhen Zhang、Yanchun Yang、Saghir Hussain、Minlan He、Dequan Gui、Bing Ma、Chaojun Jing、Zhixin Qiao、Changjin Zhu、Qun Yu

  DOI：10.1016/j.bmc.2011.07.051

  日期：2011.12

  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.
• Selective synthesis and comparative activity of olefinic isomers of 1,2-benzothiazine-1,1-dioxide carboxylates as aldose reductase inhibitors
  作者：Shagufta Parveen、Saghir Hussain、Shaojuan Zhu、Xiangyu Qin、Xin Hao、Shuzhen Zhang、Jianglu Lu、Changjin Zhu

  DOI：10.1039/c4ra01016g

  日期：——

  α,β- and β,γ-unsaturated carboxylate isomers of 1,2-benzothiazine-1,1-dioxide were selectively synthesized via the Wittig olefination reaction under various temperature conditions. At 40 °C, α,β-unsaturated esters with high Z-stereoselectivity (83–87%) were formed, while β,γ-unsaturated esters formed preferentially with moderate to excellent regioselectivity at 100–120 °C (77–96%). The acid isomers

  通过Wittig烯化反应在各种温度条件下选择性合成1,2-苯并噻嗪-1,1-二氧化物的α，β-和β，γ-不饱和羧酸酯异构体。在40°C时，会形成具有高Z立体选择性（83–87％）的α，β-不饱和酯，而在100–120°C（77–96％）时，会优先形成具有中等至优异区域选择性的β，γ-不饱和酯。 ）。发现酸异构体按活性β，γ-不饱和> Z -α，β-不饱和> E -α，β-不饱和异构体的顺序抑制醛糖还原酶。β，γ-不饱和异构体7b，2- [2-（4-溴-2-氟苄基）-1,1-二氧化物2 H -1,2-苯并噻嗪-4（3 H）-亚烷基]乙酸具有最强的抑制活性，IC 50值为0.057μM。对接研究进一步支持了这一点。