4-[2-[Benzyl-[2-hydroxy-2-[3-(hydroxymethyl)-4-phenylmethoxyphenyl]ethyl]amino]ethyl]phenol | 630127-12-7

• 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: 4-[2-[Benzyl-[2-hydroxy-2-[3-(hydroxymethyl)-4-phenylmethoxyphenyl]ethyl]amino]ethyl]phenol
• CAS: 630127-12-7
• 化学式: C₃₁H₃₃NO₄
• 分子量: 483.607
• InChiKey: ODKDWESCASGLSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[2-[Benzyl-[2-hydroxy-2-[3-(hydroxymethyl)-4-phenylmethoxyphenyl]ethyl]amino]ethyl]phenol 在 sodium tetrahydroborate 、 5%-palladium/activated carbon 、 氢气 、 caesium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 12.0h， 生成 4-[1-Hydroxy-2-[2-[4-(2-hydroxy-2-phenylethoxy)phenyl]ethylamino]ethyl]-2-(hydroxymethyl)phenol
  参考文献：
  名称：

  A multivalent approach to the discovery of long-acting β2-adrenoceptor agonists for the treatment of asthma and COPD

  摘要：

  A multivalent approach was applied to the design of long-acting inhaled beta(2)-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting beta(2)-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C-2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding Potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.072
• 作为产物：
  描述：

  5-乙酰水杨酸甲酯 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 溴 、 碳酸氢钠 、 potassium carbonate 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 4-[2-[Benzyl-[2-hydroxy-2-[3-(hydroxymethyl)-4-phenylmethoxyphenyl]ethyl]amino]ethyl]phenol
  参考文献：
  名称：

  A multivalent approach to the discovery of long-acting β2-adrenoceptor agonists for the treatment of asthma and COPD

  摘要：

  A multivalent approach was applied to the design of long-acting inhaled beta(2)-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting beta(2)-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C-2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding Potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.072

文献信息

• [EN] ALKOXY ARYL beta2 ADRENERGIC RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RECEPTEUR ADRENERGIQUE DOLLAR G(B)2 ALCOXY ARYLE
  申请人：THERAVANCE INC

  公开号：WO2003099764A1

  公开（公告）日：2003-12-04

  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 β2 adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.

  该发明提供了新型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疾病的方法，以及用于制备这些化合物的过程和中间体。
• A multivalent approach to the discovery of long-acting β2-adrenoceptor agonists for the treatment of asthma and COPD
  作者：John R. Jacobsen、Seok Ki Choi、Jesse Combs、Eric J.L. Fournier、Uwe Klein、Juergen W. Pfeiffer、G. Roger Thomas、Cecile Yu、Edmund J. Moran

  DOI：10.1016/j.bmcl.2011.11.072

  日期：2012.1

  A multivalent approach was applied to the design of long-acting inhaled beta(2)-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting beta(2)-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C-2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding Potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection. (C) 2011 Elsevier Ltd. All rights reserved.