4-(4-bromo-2-fluorobenzyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide | 1256768-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 4-(4-bromo-2-fluorobenzyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 4-[(4-Bromo-2-fluorophenyl)methyl]-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide；4-[(4-bromo-2-fluorophenyl)methyl]-2,3-dihydro-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 1256768-92-9
• 化学式: C₁₄H₁₂BrFN₂O₂S
• 分子量: 371.23
• InChiKey: BQEXYFYGWNKGAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-2-fluorobenzyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 、 溴乙酸甲酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以86%的产率得到[4-(4-bromo-2-fluorobenzyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-2-yl]acetic acid methyl ester
  参考文献：
  名称：

  Acetic Acid Derivatives of 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxide as a Novel Class of Potent Aldose Reductase Inhibitors

  摘要：

  A series of novel benzothiadiazine 1,1-dioxide derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Of these derivatives, 17 compounds, having a substituted N2-benzyl group and a N4-acetic acid group on the benzothiadiazine, were found to be potent and selective aldose reductase inhibitors in vitro with IC50 values ranging from 0.032 to 0.975 mu M. 9m proved to be the most active in vitro. The eight top-scoring compounds coming from the in vitro test for ALR2 inhibition activity were then tested in vivo, whereby three derivatives, 9i, 9j, and 9m, demonstrated a significantly preventive effect on sorbitol accumulation in the sciatic nerve in the 5-day streptozotocin-induced diabetic rats in vivo. Structure activity relationship and molecular docking studies highlighted the importance of substitution features of N4-acetic acid group and halogen-substituted N2-benzyl group in the benzothiadiazine scaffold and indicated that substitution with hallogen at C-7 had a remarkably strong effect on ALR2 inhibition potency.

  DOI：

  10.1021/jm100962a
• 作为产物：
  描述：

  4-(4-bromo-2-fluorobenzyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide 在 sodium tetrahydroborate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 0.08h， 以70%的产率得到4-(4-bromo-2-fluorobenzyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Acetic Acid Derivatives of 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxide as a Novel Class of Potent Aldose Reductase Inhibitors

  摘要：

  A series of novel benzothiadiazine 1,1-dioxide derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Of these derivatives, 17 compounds, having a substituted N2-benzyl group and a N4-acetic acid group on the benzothiadiazine, were found to be potent and selective aldose reductase inhibitors in vitro with IC50 values ranging from 0.032 to 0.975 mu M. 9m proved to be the most active in vitro. The eight top-scoring compounds coming from the in vitro test for ALR2 inhibition activity were then tested in vivo, whereby three derivatives, 9i, 9j, and 9m, demonstrated a significantly preventive effect on sorbitol accumulation in the sciatic nerve in the 5-day streptozotocin-induced diabetic rats in vivo. Structure activity relationship and molecular docking studies highlighted the importance of substitution features of N4-acetic acid group and halogen-substituted N2-benzyl group in the benzothiadiazine scaffold and indicated that substitution with hallogen at C-7 had a remarkably strong effect on ALR2 inhibition potency.

  DOI：

  10.1021/jm100962a

文献信息

• Acetic Acid Derivatives of 3,4-Dihydro-2<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxide as a Novel Class of Potent Aldose Reductase Inhibitors
  作者：Xin Chen、Changjin Zhu、Fan Guo、Xiaowei Qiu、Yanchun Yang、Shuzhen Zhang、Minlan He、Shagufta Parveen、Chaojun Jing、Yan Li、Bing Ma

  DOI：10.1021/jm100962a

  日期：2010.12.9

  A series of novel benzothiadiazine 1,1-dioxide derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Of these derivatives, 17 compounds, having a substituted N2-benzyl group and a N4-acetic acid group on the benzothiadiazine, were found to be potent and selective aldose reductase inhibitors in vitro with IC50 values ranging from 0.032 to 0.975 mu M. 9m proved to be the most active in vitro. The eight top-scoring compounds coming from the in vitro test for ALR2 inhibition activity were then tested in vivo, whereby three derivatives, 9i, 9j, and 9m, demonstrated a significantly preventive effect on sorbitol accumulation in the sciatic nerve in the 5-day streptozotocin-induced diabetic rats in vivo. Structure activity relationship and molecular docking studies highlighted the importance of substitution features of N4-acetic acid group and halogen-substituted N2-benzyl group in the benzothiadiazine scaffold and indicated that substitution with hallogen at C-7 had a remarkably strong effect on ALR2 inhibition potency.