(R)-5-(2-((4-((4-(4-aminobutoxy)phenyl)amino)phenethyl)amino)-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one | 1613189-34-6

• 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: (R)-5-(2-((4-((4-(4-aminobutoxy)phenyl)amino)phenethyl)amino)-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one
• CAS: 1613189-34-6
• 化学式: C₄₂H₅₄N₄O₄Si
• 分子量: 707.001
• InChiKey: SLJJBESOPFZOHW-KDXMTYKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.86
• 重原子数：
  51.0
• 可旋转键数：
  18.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  110.63
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (R)-5-(2-((4-((4-(4-aminobutoxy)phenyl)amino)phenethyl)amino)-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one 在 triethylamine tris(hydrogen fluoride) 作用下， 以 乙醇 、 异丙醇 为溶剂， 生成
  参考文献：
  名称：

  Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD

  摘要：

  A multivalent approach focused on amine-based secondary binding groups was applied to the discovery of long-acting inhaled beta(2)-agonists. Addition of amine moieties to the neutral secondary binding group of an existing beta(2)-agonist series was found to provide improved in vivo efficacy, but also led to the formation of biologically active aldehyde metabolites which were viewed as a risk for the development of these compounds. Structural simplification of the scaffold and blocking the site of metabolism to prevent aldehyde formation afforded a potent series of dibasic beta(2)-agonists with improved duration of action relative to their monobasic analogs. Additional optimization led to the discovery of 29 (TD-4306), a potent and selective beta(2)-agonist with potential for once-daily dosing. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.095
• 作为产物：
  描述：

  4-溴苯乙胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 生成 (R)-5-(2-((4-((4-(4-aminobutoxy)phenyl)amino)phenethyl)amino)-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one
  参考文献：
  名称：

  Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD

  摘要：

  A multivalent approach focused on amine-based secondary binding groups was applied to the discovery of long-acting inhaled beta(2)-agonists. Addition of amine moieties to the neutral secondary binding group of an existing beta(2)-agonist series was found to provide improved in vivo efficacy, but also led to the formation of biologically active aldehyde metabolites which were viewed as a risk for the development of these compounds. Structural simplification of the scaffold and blocking the site of metabolism to prevent aldehyde formation afforded a potent series of dibasic beta(2)-agonists with improved duration of action relative to their monobasic analogs. Additional optimization led to the discovery of 29 (TD-4306), a potent and selective beta(2)-agonist with potential for once-daily dosing. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.095