(S)-2-(3,5-bis(benzyloxy)phenyl)oxirane | 103145-40-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-2-(3,5-bis(benzyloxy)phenyl)oxirane
• 英文别名: (2S)-2-[3,5-bis(phenylmethoxy)phenyl]oxirane
• CAS: 103145-40-0
• 化学式: C₂₂H₂₀O₃
• 分子量: 332.399
• InChiKey: IXYYQIMVOHFSDN-JOCHJYFZSA-N

物化性质

• 沸点：
  501.5±50.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-(3,5-bis(benzyloxy)phenyl)oxirane 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 120.0 ℃ 、344.75 kPa 条件下， 反应 44.0h， 生成 (S,R)-5-(1-hydroxy-2-{[2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)benzene-1,3-diol
  参考文献：
  名称：

  Comparative Molecular Field Analysis of the Binding of the Stereoisomers of Fenoterol and Fenoterol Derivatives to the β₂ Adrenergic Receptor

  摘要：

  Stereoisomers of fenoterol and six fenoterol derivatives have been synthesized and their binding affinities for the beta(2) adrenergic receptor (K-i beta(2)-AR), the subtype selectivity relative to the beta(1)-AR (K-i beta(1)-AR/K-i beta(2)-AR) and their functional activities were determined. Of the 26 compounds synthesized in the study, submicromolar binding affinities were observed for (R,R)-fenoterol, the (R,R)-isomer of the p-methoxy, and (R,R)- and (R,S)-isomers of 1-naphthyl derivatives and all of these compounds were active at submicromolar concentrations in cardiomyocyte contractility tests. The K-i beta(1)-AR/K-i beta(2)-AR ratios were > 40 for (R,R)-fenoterol and the (R,R)-p-methoxy and (R,S)-1-naphthyl derivatives and 14 for the (R,R)-1-napthyl derivative. The binding data was analyzed using comparative molecular field analysis (CoMFA), and the resulting model indicated that the fenoterol derivatives interacted with two separate binding sites and one steric restricted site on the pseudo-receptor and that the chirality of the second stereogenic center affected K-i beta(2) and subtype selectivity.

  DOI：

  10.1021/jm070030d
• 作为产物：
  描述：

  2-溴-1-(3,5-二(苄氧基)苯基)乙醇 在 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 (S)-2-(3,5-bis(benzyloxy)phenyl)oxirane
  参考文献：
  名称：

  Use of fenoterol and fenoterol analogues in the treatment of glioblastomas and astrocytomas

  摘要：

  这项披露涉及发现使用非托罗尔和(R,R)-和(R,S)-非托罗尔类似物治疗表达β2肾上腺素受体的肿瘤，例如表达β2肾上腺素受体的原发性脑肿瘤，包括表达β2肾上腺素受体的胶质母细胞瘤或星形细胞瘤。在一个示例中，该方法包括向受试者施用治疗有效量的非托罗尔、特定的非托罗尔类似物或其组合，以减少与肿瘤相关的一个或多个症状，从而治疗受试者的肿瘤。

  公开号：

  US09492405B2

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.