8-benzyloxy-5-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-2-(2-{4-[4-(2-piperazin-1-yl-ethoxy)-phenylamino]-phenyl}-ethylamino)-ethyl]-1H-quinolin-2-one | 1008423-34-4

• 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-benzyloxy-5-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-2-(2-{4-[4-(2-piperazin-1-yl-ethoxy)-phenylamino]-phenyl}-ethylamino)-ethyl]-1H-quinolin-2-one
• 英文别名: 5-[(1R)-1-[tert-butyl(dimethyl)silyl]oxy-2-[2-[4-[4-(2-piperazin-1-ylethoxy)anilino]phenyl]ethylamino]ethyl]-8-phenylmethoxy-1H-quinolin-2-one
• CAS: 1008423-34-4
• 化学式: C₄₄H₅₇N₅O₄Si
• 分子量: 748.053
• InChiKey: BQHBNRDYTFIJSB-RWYGWLOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.03
• 重原子数：
  54
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  96.1
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-benzyloxy-5-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-2-(2-{4-[4-(2-piperazin-1-yl-ethoxy)-phenylamino]-phenyl}-ethylamino)-ethyl]-1H-quinolin-2-one 在 氢气 、 palladium(II) hydroxide 、 triethylamine tris(hydrogen fluoride) 作用下， 以 乙醇 、 异丙醇 为溶剂， 生成 8-hydroxy-5-[(R)-1-hydroxy-2-(2-{4-[4-(2-piperazin-1-yl-ethoxy)-phenylamino]-phenyl}-ethylamino)-ethyl]-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
• 作为产物：
  描述：

  8-苄氧基-5-[(1R)-2-溴-1-[叔丁基二甲基硅基]氧代-乙基]-1H-喹啉-2-酮 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 8-benzyloxy-5-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-2-(2-{4-[4-(2-piperazin-1-yl-ethoxy)-phenylamino]-phenyl}-ethylamino)-ethyl]-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

• Aryl aniline derivatives as beta2 adrenergic receptor agonists
  申请人：McKinnell M. Robert

  公开号：US20050159448A1

  公开（公告）日：2005-07-21

  The invention provides novel β 2 adrenergic receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with β 2 adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.

  这项发明提供了新型的β2肾上腺素受体激动剂化合物。该发明还提供了包含这些化合物的药物组合物，使用这些化合物治疗与β2肾上腺素受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。
• 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.