1-(5-ethyl-2-hydroxy-4-((7-methyl-7-(1H-tetrazol-5-yl)octyl)oxy)phenyl)ethanone | 140660-17-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(5-ethyl-2-hydroxy-4-((7-methyl-7-(1H-tetrazol-5-yl)octyl)oxy)phenyl)ethanone
• 英文别名: 1-[5-ethyl-2-hydroxy-4-[7-methyl-7-(2H-tetrazol-5-yl)octoxy]phenyl]ethanone
• CAS: 140660-17-9
• 化学式: C₂₀H₃₀N₄O₃
• 分子量: 374.483
• InChiKey: FFBXXZSZNZOOBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-乙基间苯二酚 在 叠氮基三甲基硅烷 、 potassium carbonate 、 tetra-n-butylammoniumfluoride trihydrate 、 potassium iodide 、 zinc(II) chloride 作用下， 以 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 56.0h， 生成 1-(5-ethyl-2-hydroxy-4-((7-methyl-7-(1H-tetrazol-5-yl)octyl)oxy)phenyl)ethanone
  参考文献：
  名称：

  Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists

  摘要：

  Compound 1 (IC50 = 35.2 +/- 7.2 mu M), a moderate FXR antagonist was discovered via high-throughput screening. Structure-activity relationship studies indicated that the shape and the lipophilicity of the substituents of the aromatic ring affect the activity dramatically, increasing the shape and the lipophilicity of the substituents of the aromatic ring enhances the potency of FXR antagonists. Especially, when the OH at C2 position of the aromatic ring was replaced by the OBn substituent (analog 2b), its activity could be improved to IC50 = 1.1 +/- 0.1 mu M. Besides, the length of the linker and the tetrazole structure are essential for retaining the activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.032

文献信息

• Leukotriene B4 receptor antagonists: the LY255283 series of hydroxyacetophenones
  作者：David K. Herron、Theodore Goodson、Nancy G. Bollinger、Dorothy Swanson-Bean、Ian G. Wright、Gilbert S. Staten、Alan R. Thompson、Larry L. Froelich、William T. Jackson

  DOI：10.1021/jm00088a018

  日期：1992.5

  A series of hydroxyacetophenones was prepared for evaluation as leukotriene B4 (LTB4) receptor antagonists, culminating in 1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5- yl)heptyl]oxy]phenyl]ethanone (compound 35, LY255283). Using an assay for inhibition of specific [3H]LTB4 binding to human PMN, we found that substitution of a nonpolar substituent in the 5-position was required for activity.

  制备了一系列羟基苯乙酮作为白三烯B4（LTB4）受体拮抗剂进行评估，最终以1- [5-乙基-2-羟基-4-[[6-甲基-6-（1H-四唑-5-基）庚基] [氧基]苯基]乙酮（化合物35，LY255283）。使用抑制特异性[3H] LTB4与人PMN结合的测定方法，我们发现活性需要5位非极性取代基的取代。最佳活性是通过3位氢，2位羟基，1位短链烷基酮以及将4位氧与不饱和末端相连的六碳或八碳链实现的功能。选择在结合试验中IC50为87 nM的化合物35进行进一步的临床前评估。