[2-(3-nitrobenzyl)-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-4-yl]acetic acid methyl ester | 1256768-44-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [2-(3-nitrobenzyl)-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-4-yl]acetic acid methyl ester
• 英文别名: methyl 2-[7-fluoro-2-[(3-nitrophenyl)methyl]-1,1-dioxo-3H-1lambda6,2,4-benzothiadiazin-4-yl]acetate；methyl 2-[7-fluoro-2-[(3-nitrophenyl)methyl]-1,1-dioxo-3H-1λ6,2,4-benzothiadiazin-4-yl]acetate
• CAS: 1256768-44-1
• 化学式: C₁₇H₁₆FN₃O₆S
• 分子量: 409.395
• InChiKey: UHGFTMBHGOZAKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [2-(3-nitrobenzyl)-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-4-yl]acetic acid methyl ester 在 氨 作用下， 以 甲醇 为溶剂， 以89%的产率得到[2-(3-nitrobenzyl)-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-4-yl]acetamide
  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：

  (7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-4-yl)acetic acid methyl ester 、 3-硝基溴苄 在 potassium carbonate 作用下， 以 acetonitrle 为溶剂， 反应 2.0h， 以81%的产率得到[2-(3-nitrobenzyl)-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-4-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