4-(3-allyl-5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-1-methyl-6-(trifluoromethyl)quinolin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(3-allyl-5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-1-methyl-6-(trifluoromethyl)quinolin-2(1H)-one
• 英文别名: 4-(5-Chloro-2-hydroxy-3-prop-2-enylphenyl)-3-(2-hydroxyethyl)-1-methyl-6-(trifluoromethyl)quinolin-2-one
• 化学式: C₂₂H₁₉ClF₃NO₃
• 分子量: 437.846
• InChiKey: GDIMORZTBARRSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(3-allyl-5-chloro-2-hydroxyphenyl)-3-(2-(tert-butyldiphenylsilyloxy)ethyl)-1-methyl-6-(trifluoromethyl)quinolin-2(1H)-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以81%的产率得到4-(3-allyl-5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-1-methyl-6-(trifluoromethyl)quinolin-2(1H)-one
  参考文献：
  名称：

  Atropisomeric 3-(β-hydroxyethyl)-4-arylquinolin-2-ones as Maxi-K Potassium Channel Openers

  摘要：

  The synthesis of a series of 3-beta-hydroxyethyl-4-arylquinolin-2-ones is described. These compounds contain hydrophilic and hydrophobic substituents ortho to the phenolic OH in the C ring of the quinolinone. Electrophysiological evaluation of the panel of compounds revealed that 11 and 16 with an unbranched ortho substituent retain activity as maxi-K ion channel openers. Members of this series of compounds can exist as stable atropisomers. Calculated estimates of the energy barrier for rotation around the aryl-aryl single bond in 3 is 31 kcal/mol. The atropisomers of (+/-)-3, (+/-)-4, and (+/-)-11 were separated by chiral HPLC and tested for their effect on maxi-K mediated outward current in hSlo injected X. laevis oocytes. The (-) isomer in each case was found to be more active than the corresponding (+) isomer, suggesting that the ion channel exhibits stereoselective activation. X-ray crystallographic structures of (+)-3 and (+)-11 were determined. Evaluation of the stability of (-)-3 at 80 degrees C in n-butanol indicated a 19.6% conversion to (+)-3 over 72 h. In human serum at 37 degrees C (-)-3 did not racemize over the course of the 30 h study.

  DOI：

  10.1021/jm061093j