ethyl 2-[(6-(2-ethoxy-2-oxoethoxy)-2-oxo-2H-chromen-7-yl)oxy]acetate

• 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 2-[(6-(2-ethoxy-2-oxoethoxy)-2-oxo-2H-chromen-7-yl)oxy]acetate
• 英文别名: ethyl {[6-(2-ethoxy-2-oxoethoxy)-2-oxo-2H-chromen-7-yl]oxy}acetate；Ethyl 2-[7-(2-ethoxy-2-oxoethoxy)-2-oxochromen-6-yl]oxyacetate
• 化学式: C₁₇H₁₈O₈
• 分子量: 350.325
• InChiKey: UBWMUTZDGDINDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  6,7-二羟基香豆素 、 溴乙酸乙酯 在 potassium carbonate 作用下， 以 丙酮 、 乙酸乙酯 为溶剂， 反应 6.5h， 以91%的产率得到ethyl 2-[(6-(2-ethoxy-2-oxoethoxy)-2-oxo-2H-chromen-7-yl)oxy]acetate
  参考文献：
  名称：

  Semisynthesis, ex vivo evaluation, and SAR studies of coumarin derivatives as potential antiasthmatic drugs

  摘要：

  Asthma is a chronic inflammatory disorder that causes contraction in the smooth muscle of the airway and blocking of airflow. Reversal the contractile process is a strategy for the search of new drugs that could be used for the treatment of asthma. This work reports the semisynthesis, ex vivo relaxing evaluation and SAR studies of a series of 18 coumarins. The results pointed that the ether derivatives 1-3, 7-9 and 13-15 showed the best activity (E-max = 100%), where compound 2 (42 mu M) was the most potent, being 4-times more active than theophylline (positive control). The ether homologation (methyl, ethyl and propyl) in position 7 or positions 6 and 7 of coumarins lead to relaxing effect, meanwhile formation of esters generated less active compounds than ethers. The SAR analysis showed that it is necessary the presence of two small ether groups and the methyl group at position 4 (site 3) encourage biological activity through soft hydrophobic changes in the molecule, without drastically affecting the cLogP. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.029

文献信息

• A new convenient route to 2-oxoethoxycoumarins: key intermediates in the synthesis of natural products
  作者：Stefano Chimichi、Marco Boccalini、Barbara Cosimelli

  DOI：10.1016/s0040-4020(02)00442-8

  日期：2002.6

  A new synthetic route to coumarinyloxyaldehydes starting from hydroxycoumarins is presented; these compounds, useful intermediates in the preparation of natural products such as geiparvarin and psoralens, are now available in excellent yields with a simple workup procedure. Moreover the reported route has been applied to dihydroxycoumarins.

  提出了一种从羟基香豆素开始合成香豆素氧基醛的新方法。这些化合物是制备天然产物（如geiparvarin和补骨脂素）中有用的中间体，现在可以通过简单的后处理程序以高收率获得。此外，所报道的途径已经应用于二羟基香豆素。
• Semisynthesis, ex vivo evaluation, and SAR studies of coumarin derivatives as potential antiasthmatic drugs
  作者：Amanda Sánchez-Recillas、Gabriel Navarrete-Vázquez、Sergio Hidalgo-Figueroa、María Yolanda Rios、Maximiliano Ibarra-Barajas、Samuel Estrada-Soto

  DOI：10.1016/j.ejmech.2014.03.029

  日期：2014.4

  Asthma is a chronic inflammatory disorder that causes contraction in the smooth muscle of the airway and blocking of airflow. Reversal the contractile process is a strategy for the search of new drugs that could be used for the treatment of asthma. This work reports the semisynthesis, ex vivo relaxing evaluation and SAR studies of a series of 18 coumarins. The results pointed that the ether derivatives 1-3, 7-9 and 13-15 showed the best activity (E-max = 100%), where compound 2 (42 mu M) was the most potent, being 4-times more active than theophylline (positive control). The ether homologation (methyl, ethyl and propyl) in position 7 or positions 6 and 7 of coumarins lead to relaxing effect, meanwhile formation of esters generated less active compounds than ethers. The SAR analysis showed that it is necessary the presence of two small ether groups and the methyl group at position 4 (site 3) encourage biological activity through soft hydrophobic changes in the molecule, without drastically affecting the cLogP. (C) 2014 Elsevier Masson SAS. All rights reserved.