N-{5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-2-hydroxy-phenyl}-formamide | 860032-54-8

• 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-hydroxy-ethyl]-2-hydroxy-phenyl}-formamide
• 英文别名: N-[5-[(1R)-2-[2-[4-[4-(2-amino-2-methylpropoxy)anilino]phenyl]ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]formamide
• CAS: 860032-54-8
• 化学式: C₂₇H₃₄N₄O₄
• 分子量: 478.591
• InChiKey: BOGKGWCOWBCLCB-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 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：

  (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane 在 氢气 、 palladium(II) hydroxide 、 potassium carbonate 、 triethylamine tris(hydrogen fluoride) 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 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-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

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。
• ARYL ANILINE DERIVATIVES AS BETA2 ADRENERGIC RECEPTOR AGONISTS
  申请人：McKinnell Robert M.

  公开号：US20100087410A1

  公开（公告）日：2010-04-08

  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.

  本发明提供了新型的β2肾上腺素能受体激动剂化合物。本发明还提供包含这些化合物的药物组合物，使用这些化合物治疗与β2肾上腺素能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。
• US7622467B2
  申请人：——

  公开号：US7622467B2

  公开（公告）日：2009-11-24
• US7994165B2
  申请人：——

  公开号：US7994165B2

  公开（公告）日：2011-08-09
• [EN] ARYL ANILINE DERIVATIVES AS BETA2 ADRENERGIC RECEPTOR AGONISTS<br/>[FR] DERIVES D'ARYLANILINE UTILISE COMME AGONISTES DES RECEPTEURS BETA2-ADRENERGIQUES
  申请人：THERAVANCE INC

  公开号：WO2005070872A1

  公开（公告）日：2005-08-04

  The invention provides novel β2-adrenergic receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with β2-adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.