ethyl 3-{7-[(bromoacetyl)oxy]-4-methyl-2-oxo-2H-chromen-3-yl}propanoate | 1048691-54-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: ethyl 3-{7-[(bromoacetyl)oxy]-4-methyl-2-oxo-2H-chromen-3-yl}propanoate
• CAS: 1048691-54-8
• 化学式: C₁₇H₁₇BrO₆
• 分子量: 397.222
• InChiKey: IOFVOASJILRZIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  82.81
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  溴代乙酸酐 、 ethyl 3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-3-yl)propanoate 以 乙腈 为溶剂， 反应 6.0h， 生成 ethyl 3-{7-[(bromoacetyl)oxy]-4-methyl-2-oxo-2H-chromen-3-yl}propanoate
  参考文献：
  名称：

  Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4,8-dimethylcoumarins

  摘要：

  Aberrant interaction between the leukocyte and the endothelial cell (EC) resulting from the deregulated expression of cell adhesion molecules (CAMs) on the endothelium results in uncontrolled inflammation leading to various inflammatory disorders. The existing drugs used to modulate the cytokine-induced expression of cell molecules have severe side effects. Therefore, there is an unmet therapeutic need to develop potent and safe drugs to treat inflammatory disorders. In the present study, novel PEGylated and non-PEGylated 4-methyl and 4,8-dimethylcoumarin derivatives were designed, synthesized and, evaluated for ICAM-1 inhibitory activity. The PEGylated coumarins were synthesized in two different ways. In the first approach. diesters of 4-methyl and 4,8-dimethylcoumarin were co-polymerized, separately with poly(ethylene glycol) using Candida antarctica lipase under solventless conditions. In the other approach, 4-methyl and 4,8-dimethylcoumarins were suitably converted to their bromo analogues and were tethered to already synthesized PEGylated polymers. Synthesized derivatives were evaluated for anti-inflammatory activities with respect to their ability to inhibit the TNF-alpha induced ICAM-1 (intercellular cell adhesion molecule-1) on human endothelial cells. It was found that PEGylated 4-methyl and 4,8-dimethylcoumarin derivatives were more effective than their non-PEGylated analogues to inhibit ICAM-1 expression. The present study opens new vista for PEGylated non-steroidal anti-inflammatory compounds and their further investigations. (C) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2009.11.008