N-{5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-benzyloxy-phenyl}-formamide | 860032-38-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-{5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-benzyloxy-phenyl}-formamide
• 英文别名: N-[5-[(1R)-2-[2-[4-[4-(2-amino-2-methylpropoxy)anilino]phenyl]ethylamino]-1-[tert-butyl(dimethyl)silyl]oxyethyl]-2-phenylmethoxyphenyl]formamide
• CAS: 860032-38-8
• 化学式: C₄₀H₅₄N₄O₄Si
• 分子量: 682.979
• InChiKey: WXCASCNNPGTJBZ-LHEWISCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.59
• 重原子数：
  49
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-{5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-benzyloxy-phenyl}-formamide 在 氢气 、 palladium(II) hydroxide 、 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 N-{5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-2-hydroxy-phenyl}-formamide
  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：

  (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane 在 potassium carbonate 、 sodium iodide 作用下， 以 二甲基亚砜 为溶剂， 生成 N-{5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-benzyloxy-phenyl}-formamide
  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。