2-(4-fluorobenzyl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(4-fluorobenzyl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-[(4-Fluorophenyl)methyl]-3a,4,7,7a-tetrahydroisoindole-1,3-dione
• 化学式: C₁₅H₁₄FNO₂
• 分子量: 259.28
• InChiKey: RNAIGUHTRRILRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对氟苄胺 、 四氢化邻苯二甲酸酐 在 溶剂黄146 作用下， 反应 4.0h， 以78%的产率得到2-(4-fluorobenzyl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: Anti-inflammatory and analgesic activities

  摘要：

  A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.24, 0.28 and 036 AM; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure activity studies identified compound 6a as a highly potent (IC50 = 0.18 AM), and an extremely selective [COX-2 (SI) = 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 54.0 mg/kg) relative to didofenac (ED50 = 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2 degrees-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02 angstrom), Arg(513) (1.94, 2.83 angstrom), and Gln(192) (3.25 angstrom). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.039