4-[1-Hydroxy-2-[2-[4-[[2-hydroxy-2-(4-hydroxyphenyl)ethyl]amino]phenyl]ethylamino]ethyl]-2-(hydroxymethyl)phenol | 1355183-67-3

• 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-[1-Hydroxy-2-[2-[4-[[2-hydroxy-2-(4-hydroxyphenyl)ethyl]amino]phenyl]ethylamino]ethyl]-2-(hydroxymethyl)phenol
• CAS: 1355183-67-3
• 化学式: C₂₅H₃₀N₂O₅
• 分子量: 438.524
• InChiKey: WGPSKNWYOMXLRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  125
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(4-氨基苯)乙胺 在 sodium tetrahydroborate 、 borane dimethyl sulphide complex 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 28.0h， 生成 4-[1-Hydroxy-2-[2-[4-[[2-hydroxy-2-(4-hydroxyphenyl)ethyl]amino]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

文献信息

• 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.