4-oxo-2-[4-(trifluoromethyl)phenyl]methyl-1,2-dihydro-1λ⁶,2-benzothiazine-1,1(3H)-dione | 1349171-00-1

• 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: 4-oxo-2-[4-(trifluoromethyl)phenyl]methyl-1,2-dihydro-1λ⁶,2-benzothiazine-1,1(3H)-dione
• 英文别名: 2-[4-(trifluoromethyl)benzyl]-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide；1,1-dioxo-2-[[4-(trifluoromethyl)phenyl]methyl]-3H-1lambda6,2-benzothiazin-4-one；1,1-dioxo-2-[[4-(trifluoromethyl)phenyl]methyl]-3H-1λ6,2-benzothiazin-4-one
• CAS: 1349171-00-1
• 化学式: C₁₆H₁₂F₃NO₃S
• 分子量: 355.337
• InChiKey: UMBYHXPUBZOEIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  4-oxo-2-[4-(trifluoromethyl)phenyl]methyl-1,2-dihydro-1λ⁶,2-benzothiazine-1,1(3H)-dione 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 14.0h， 生成 2-[2-(4-(trifluoromethyl)benzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid
  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：

  saccharin sodium salt 在 盐酸 、 硫酸 、 水 、 sodium methylate 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 50.0h， 生成 4-oxo-2-[4-(trifluoromethyl)phenyl]methyl-1,2-dihydro-1λ⁶,2-benzothiazine-1,1(3H)-dione
  参考文献：
  名称：

  N-杂环卡宾有机催化[3+3]环化反应选择性合成苯并吡喃噻嗪酮

  摘要：

  该设计受奥昔康核心结构的启发，允许采用 N-杂环卡宾 (NHC) 催化对映选择性合成苯并吡喃噻嗪酮基序。 NHC 介导的转化涉及 α,β-不饱和醛与合适的取代苯并噻嗪酮衍生物的反应。该过程包括从炔醛初始形成 α,β-不饱和酰唑鎓，同时从苯并噻嗪酮生成烯醇化物。这些反应的最终结果是有效的环化，产生具有合理产率和高立体选择性的所需产物。这项研究强调了 NHC 催化在简化复杂杂环结构合成中的潜力。

  DOI：

  10.1002/adsc.202301082

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。
• 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.
• N‐Heterocyclic Carbene Organocatalyzed [3+3] Annulation for the Enantioselective Synthesis of Benzopyranothiazinones
  作者：Karina Mroczyńska、Zbigniew Rafiński

  DOI：10.1002/adsc.202301082

  日期：2024.3.19

  The design, inspired by the core-structure of oxicam has allowed the enantioselective synthesis of benzopyranothiazinone motifs employing N-heterocyclic carbene (NHC) catalysis. The NHC-mediated transformation involves the reaction of α,β-unsaturated aldehydes with suitable substituted benzothiazinone derivatives. This process encompasses the initial formation of α,β-unsaturated acylazoliums from ynals

  该设计受奥昔康核心结构的启发，允许采用 N-杂环卡宾 (NHC) 催化对映选择性合成苯并吡喃噻嗪酮基序。 NHC 介导的转化涉及 α,β-不饱和醛与合适的取代苯并噻嗪酮衍生物的反应。该过程包括从炔醛初始形成 α,β-不饱和酰唑鎓，同时从苯并噻嗪酮生成烯醇化物。这些反应的最终结果是有效的环化，产生具有合理产率和高立体选择性的所需产物。这项研究强调了 NHC 催化在简化复杂杂环结构合成中的潜力。