Ethyl 3-[4,8-dimethyl-2-oxo-7-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]chromen-3-yl]propanoate | 1415837-45-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Ethyl 3-[4,8-dimethyl-2-oxo-7-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]chromen-3-yl]propanoate
• 英文别名: ethyl 3-[4,8-dimethyl-2-oxo-7-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]chromen-3-yl]propanoate
• CAS: 1415837-45-4
• 化学式: C₃₀H₂₇F₃O₅
• 分子量: 524.537
• InChiKey: MCSSRUHAALMSFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Ethyl 3-[4,8-dimethyl-2-oxo-7-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]chromen-3-yl]propanoate 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以74%的产率得到3-[4,8-Dimethyl-2-oxo-7-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]chromen-3-yl]propanoic acid
  参考文献：
  名称：

  Coumarin-Based Inhibitors of Bacillus anthracis and Staphylococcus aureus Replicative DNA Helicase: Chemical Optimization, Biological Evaluation, and Antibacterial Activities

  摘要：

  The increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. Previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. Here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9-18-fold increased potency against Staphylococcus aureus (Sa) and Bacillus anthracis (Ba) helicases. Compounds 20 and 22 provided the best potency, with IC50 values of 3 and 1 mu M, respectively, against the DNA duplex strand-unwinding activities of both B. anthracis and S. aureus helicases without affecting the single strand DNA-stimulated ATPase activity. Selectivity index (SI = CC50/MIC) values against S. aureus and B. anthracis for compound 20 were 33 and 66 and for compound 22 were 20 and 40, respectively. In addition, compounds 20 and 22 demonstrated potent antibacterial activity against multiple ciprofloxacin-resistant MRSA strains, with MIC values ranging between 0.5 and 4.2 mu g/mL.

  DOI：

  10.1021/jm300922h
• 作为产物：
  描述：

  乙酰戊二酸二乙酯 在 盐酸 、 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 、 丙酮 为溶剂， 反应 353.0h， 生成 Ethyl 3-[4,8-dimethyl-2-oxo-7-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]chromen-3-yl]propanoate
  参考文献：
  名称：

  Coumarin-Based Inhibitors of Bacillus anthracis and Staphylococcus aureus Replicative DNA Helicase: Chemical Optimization, Biological Evaluation, and Antibacterial Activities

  摘要：

  The increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. Previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. Here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9-18-fold increased potency against Staphylococcus aureus (Sa) and Bacillus anthracis (Ba) helicases. Compounds 20 and 22 provided the best potency, with IC50 values of 3 and 1 mu M, respectively, against the DNA duplex strand-unwinding activities of both B. anthracis and S. aureus helicases without affecting the single strand DNA-stimulated ATPase activity. Selectivity index (SI = CC50/MIC) values against S. aureus and B. anthracis for compound 20 were 33 and 66 and for compound 22 were 20 and 40, respectively. In addition, compounds 20 and 22 demonstrated potent antibacterial activity against multiple ciprofloxacin-resistant MRSA strains, with MIC values ranging between 0.5 and 4.2 mu g/mL.

  DOI：

  10.1021/jm300922h