5-[(1R)-2-[2-[4-[4-(2-amino-2-methylpropoxy)-3-phenylanilino]phenyl]ethylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one | 1613189-25-5

• 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: 5-[(1R)-2-[2-[4-[4-(2-amino-2-methylpropoxy)-3-phenylanilino]phenyl]ethylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one
• CAS: 1613189-25-5
• 化学式: C₃₅H₃₈N₄O₄
• 分子量: 578.711
• InChiKey: HJLOLWXGFOKVSM-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  129
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氟-5-硝基联苯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 palladium(II) hydroxide 、 sodium hydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 triethylamine tris(hydrogen fluoride) 、 sodium t-butanolate 作用下， 以 甲醇 、 乙醇 、 二甲基亚砜 、 异丙醇 、 甲苯 为溶剂， 生成 5-[(1R)-2-[2-[4-[4-(2-amino-2-methylpropoxy)-3-phenylanilino]phenyl]ethylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-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

文献信息

• Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD
  作者：R. Murray McKinnell、Uwe Klein、Martin S. Linsell、Edmund J. Moran、Matthew B. Nodwell、Juergen W. Pfeiffer、G. Roger Thomas、Cecile Yu、John R. Jacobsen

  DOI：10.1016/j.bmcl.2014.04.095

  日期：2014.7

  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.