8-hydroxy-5-(2-hydroxy-1-((6-(4-phenylbutoxy)hexyl)amino)ethyl)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: 8-hydroxy-5-(2-hydroxy-1-((6-(4-phenylbutoxy)hexyl)amino)ethyl)quinolin-2(1H)-one
• 英文别名: 8-hydroxy-5-[2-hydroxy-1-[6-(4-phenylbutoxy)hexylamino]ethyl]-1H-quinolin-2-one
• 化学式: C₂₇H₃₆N₂O₄
• 分子量: 452.594
• InChiKey: ABARJLSHDALLBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  90.8
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)quinolin-2(1H)-one 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 zinc(II) chloride 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 生成 8-hydroxy-5-(2-hydroxy-1-((6-(4-phenylbutoxy)hexyl)amino)ethyl)quinolin-2(1H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of β2-adrenoceptor agonists bearing the 2-amino-2-phenylethanol scaffold

  摘要：

  A new series of beta(2)-adrenoceptor agonists bearing the 2-amino-2-phenylethanol scaffold was synthesized. Evaluation of the compounds using cell assays and an in vitro guinea pig trachea relaxation assay showed that 8-hydroxy-5-(2-hydroxy-1-((4-hydroxyphenethyl)amino)ethyl)quinolin-2(1H)-one (compound 5j) has the best pharmacological profile among all the evaluated compounds. The (S)-isomer of 5j was subsequently found to be the active enantiomer with a promising EC50 value of 1.26 nM in stimulating beta(2)-adrenoceptor-mediated cAMP accumulation and a substantially higher selectivity for the beta(2) than for the beta(1) subtype. The putative binding mode of (S)-5j revealed by molecular docking of the beta(2)-adrenoceptor resembles that in agonist binding. Taken together, these results showed that compound (S) -5j is a promising compound worthy of further study for the development of beta(2)-adrenoceptor agonists. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.04.041