(R,S′)-5-(1-hydroxy-2-((1-(4-methoxyphenyl)pentan-2-yl)amino)ethyl)benzene-1,3-diol | 1531622-36-2

• 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: (R,S′)-5-(1-hydroxy-2-((1-(4-methoxyphenyl)pentan-2-yl)amino)ethyl)benzene-1,3-diol
• 英文别名: (R,S)-4'-methoxy-n-propylfenoterol；5-[(1R)-1-hydroxy-2-[[(2S)-1-(4-methoxyphenyl)pentan-2-yl]amino]ethyl]benzene-1,3-diol
• CAS: 1531622-36-2
• 化学式: C₂₀H₂₇NO₄
• 分子量: 345.439
• InChiKey: HOCMNYATHYZPNH-JXFKEZNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  25.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  81.95
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R,S′)-5-(1-hydroxy-2-((1-(4-methoxyphenyl)pentan-2-yl)amino)ethyl)benzene-1,3-diol 、 fumaric acid 以 甲醇 为溶剂， 以352 mg的产率得到(R,S′)-5-(1-hydroxy-2-((1-(4-methoxyphenyl)pentan-2-yl)amino)ethyl)benzene-1,3-diol hemifumarate
  参考文献：
  名称：

  Comparative molecular field analysis of fenoterol derivatives interacting with an agonist-stabilized form of the β2-adrenergic receptor

  摘要：

  The beta(2)-adrenergic receptor (beta(2)-AR) agonist [H-3]-(R,R')-methoxyfenoterol was employed as the marker ligand in displacement studies measuring the binding affinities (K-i values) of the stereoisomers of a series of 4'-methoxyfenoterol analogs in which the length of the alkyl substituent at alpha' position was varied from 0 to 3 carbon atoms. The binding affinities of the compounds were additionally determined using the inverse agonist [H-3]-CGP-12177 as the marker ligand and the ability of the compounds to stimulate cAMP accumulation, measured as EC50 values, were determined in HEK293 cells expressing the beta(2)-AR. The data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the alpha' position. The results also indicate that the K-i values obtained using [H-3]-(R,R')methoxyfenoterol as the marker ligand modeled the EC50 values obtained from cAMP stimulation better than the data obtained using [H-3]-CGP-12177 as the marker ligand. The data from this study was combined with data from previous studies and processed using the Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting the binding to the beta(2)-AR conformation probed by [H-3]-(R,R')-4'-methoxyfenoterol. The CoMFA model of the agonist-stabilized beta(2)-AR suggests that the binding of the fenoterol analogs to an agonist-stabilized conformation of the beta(2)-AR is governed to a greater extend by steric effects than binding to the [H-3]-CGP-12177-stabilized conformation(s) in which electrostatic interactions play a more predominate role. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.030
• 作为产物：
  描述：

  L-正缬氨酸 在 盐酸 、 正丁基锂 、 sodium azide 、 dimethyl sulfide borane 、 palladium 10% on activated carbon 、 palladium on activated charcoal 、 氢气 、 三乙酰氧基硼氢化钠 、 三乙胺 、 potassium hydroxide 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， -70.0~135.0 ℃ 、344.75 kPa 条件下， 反应 84.58h， 生成 (R,S′)-5-(1-hydroxy-2-((1-(4-methoxyphenyl)pentan-2-yl)amino)ethyl)benzene-1,3-diol
  参考文献：
  名称：

  Comparative molecular field analysis of fenoterol derivatives interacting with an agonist-stabilized form of the β2-adrenergic receptor

  摘要：

  The beta(2)-adrenergic receptor (beta(2)-AR) agonist [H-3]-(R,R')-methoxyfenoterol was employed as the marker ligand in displacement studies measuring the binding affinities (K-i values) of the stereoisomers of a series of 4'-methoxyfenoterol analogs in which the length of the alkyl substituent at alpha' position was varied from 0 to 3 carbon atoms. The binding affinities of the compounds were additionally determined using the inverse agonist [H-3]-CGP-12177 as the marker ligand and the ability of the compounds to stimulate cAMP accumulation, measured as EC50 values, were determined in HEK293 cells expressing the beta(2)-AR. The data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the alpha' position. The results also indicate that the K-i values obtained using [H-3]-(R,R')methoxyfenoterol as the marker ligand modeled the EC50 values obtained from cAMP stimulation better than the data obtained using [H-3]-CGP-12177 as the marker ligand. The data from this study was combined with data from previous studies and processed using the Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting the binding to the beta(2)-AR conformation probed by [H-3]-(R,R')-4'-methoxyfenoterol. The CoMFA model of the agonist-stabilized beta(2)-AR suggests that the binding of the fenoterol analogs to an agonist-stabilized conformation of the beta(2)-AR is governed to a greater extend by steric effects than binding to the [H-3]-CGP-12177-stabilized conformation(s) in which electrostatic interactions play a more predominate role. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.030

文献信息

• Comparative molecular field analysis of fenoterol derivatives interacting with an agonist-stabilized form of the β2-adrenergic receptor
  作者：Anita Plazinska、Karolina Pajak、Ewelina Rutkowska、Lucita Jimenez、Joseph Kozocas、Gary Koolpe、Mary Tanga、Lawrence Toll、Irving W. Wainer、Krzysztof Jozwiak

  DOI：10.1016/j.bmc.2013.11.030

  日期：2014.1

  The beta(2)-adrenergic receptor (beta(2)-AR) agonist [H-3]-(R,R')-methoxyfenoterol was employed as the marker ligand in displacement studies measuring the binding affinities (K-i values) of the stereoisomers of a series of 4'-methoxyfenoterol analogs in which the length of the alkyl substituent at alpha' position was varied from 0 to 3 carbon atoms. The binding affinities of the compounds were additionally determined using the inverse agonist [H-3]-CGP-12177 as the marker ligand and the ability of the compounds to stimulate cAMP accumulation, measured as EC50 values, were determined in HEK293 cells expressing the beta(2)-AR. The data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the alpha' position. The results also indicate that the K-i values obtained using [H-3]-(R,R')methoxyfenoterol as the marker ligand modeled the EC50 values obtained from cAMP stimulation better than the data obtained using [H-3]-CGP-12177 as the marker ligand. The data from this study was combined with data from previous studies and processed using the Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting the binding to the beta(2)-AR conformation probed by [H-3]-(R,R')-4'-methoxyfenoterol. The CoMFA model of the agonist-stabilized beta(2)-AR suggests that the binding of the fenoterol analogs to an agonist-stabilized conformation of the beta(2)-AR is governed to a greater extend by steric effects than binding to the [H-3]-CGP-12177-stabilized conformation(s) in which electrostatic interactions play a more predominate role. (C) 2013 Elsevier Ltd. All rights reserved.