1-(2-溴乙氧基)-2-甲氧基萘 | 753022-62-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 1-(2-溴乙氧基)-2-甲氧基萘
• 英文名称: 1-(2-bromoethoxy)-2-methoxynaphthalene
• 英文别名: 1-(2-Bromoethoxy)-2-methoxynaphthalene
• CAS: 753022-62-7
• 化学式: C₁₃H₁₃BrO₂
• 分子量: 281.149
• InChiKey: YOKBIXBDJLZUQW-UHFFFAOYSA-N

物化性质

• 沸点：
  373.6±22.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-溴乙氧基)-2-甲氧基萘 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以91.3%的产率得到1-(2-azidoethoxy)-2-methoxynaphthalene
  参考文献：
  名称：

  WB4101-Related Compounds:  New, Subtype-Selective α₁-Adrenoreceptor Antagonists (or Inverse Agonists?)

  摘要：

  Our previous structure-affinity relationship study had considered the enantiomers of the naphthodioxane, tetrahydronaphthodioxane, and 2-methoxy-1-naphthoxy analogues ( compounds 1, 3, and 2, respectively) of 2-(2,6-dimethoxyphenoxyethylaminomethyl)-1,4-benzodioxane, the well-known alpha(1)-adrenoceptor (alpha(1)-AR) antagonist WB4101, showing that such modifications significantly modulate the affinity and selectivity profile for alpha(1)-AR subtypes and 5-HT1A receptor. Here, we extend investigations to antagonist activity enclosing new enantiomeric pairs, namely those of the methoxytetrahydronaphthoxy and methoxybiphenyloxy WB4101 analogues (4 and 5-7, respectively) and of a double- modified WB4101 derivative ( 8) resulting from hybridization between 2 and 3. We found that (S)-2 is a very potent (pA(2) 10.68) and moderately selective alpha(1D)-AR antagonist and the hybrid (S)-8 is a potent (pA(2) 7.98) and highly selective alpha(1A)-AR antagonist. Both of these compounds and (S)-WB4101 seem to act as inverse agonists in a vascular model. The results, which generally validate the logic we followed in designing these eight compounds, are acceptably rationalized by comparative SAR analysis of binding and functional affinities.

  DOI：

  10.1021/jm060358r
• 作为产物：
  描述：

  2-甲氧基-1-萘醛 在 lithium aluminium tetrahydride 、 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 44.0h， 生成 1-(2-溴乙氧基)-2-甲氧基萘
  参考文献：
  名称：

  Structure–affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101

  摘要：

  A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the alpha(1a)-AR with respect to the other two alpha(1), subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific alpha(1a), affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high alpha(1a) affinity of (S)-1 and its alpha(1a) versus alpha(1b) selectivity slightly increasing the alpha(1a)/alpha(1d) and alpha(1a)/5HT(1A) affinity ratios. The SAR data were evaluated in the light of known alpha(1), subtype pharmacophores and of the alpha(1a)-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.040

文献信息

• WB4101-Related Compounds:  New, Subtype-Selective α₁-Adrenoreceptor Antagonists (or Inverse Agonists?)
  作者：Marco Pallavicini、Roberta Budriesi、Laura Fumagalli、Pierfranco Ioan、Alberto Chiarini、Cristiano Bolchi、Maria Paola Ugenti、Simona Colleoni、Marco Gobbi、Ermanno Valoti

  DOI：10.1021/jm060358r

  日期：2006.11.30

  Our previous structure-affinity relationship study had considered the enantiomers of the naphthodioxane, tetrahydronaphthodioxane, and 2-methoxy-1-naphthoxy analogues ( compounds 1, 3, and 2, respectively) of 2-(2,6-dimethoxyphenoxyethylaminomethyl)-1,4-benzodioxane, the well-known alpha(1)-adrenoceptor (alpha(1)-AR) antagonist WB4101, showing that such modifications significantly modulate the affinity and selectivity profile for alpha(1)-AR subtypes and 5-HT1A receptor. Here, we extend investigations to antagonist activity enclosing new enantiomeric pairs, namely those of the methoxytetrahydronaphthoxy and methoxybiphenyloxy WB4101 analogues (4 and 5-7, respectively) and of a double- modified WB4101 derivative ( 8) resulting from hybridization between 2 and 3. We found that (S)-2 is a very potent (pA(2) 10.68) and moderately selective alpha(1D)-AR antagonist and the hybrid (S)-8 is a potent (pA(2) 7.98) and highly selective alpha(1A)-AR antagonist. Both of these compounds and (S)-WB4101 seem to act as inverse agonists in a vascular model. The results, which generally validate the logic we followed in designing these eight compounds, are acceptably rationalized by comparative SAR analysis of binding and functional affinities.
• Structure–affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101
  作者：Cristiano Bolchi、Paolo Catalano、Laura Fumagalli、Marco Gobbi、Marco Pallavicini、Alessandro Pedretti、Luigi Villa、Giulio Vistoli、Ermanno Valoti

  DOI：10.1016/j.bmc.2004.06.040

  日期：2004.9

  A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the alpha(1a)-AR with respect to the other two alpha(1), subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific alpha(1a), affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high alpha(1a) affinity of (S)-1 and its alpha(1a) versus alpha(1b) selectivity slightly increasing the alpha(1a)/alpha(1d) and alpha(1a)/5HT(1A) affinity ratios. The SAR data were evaluated in the light of known alpha(1), subtype pharmacophores and of the alpha(1a)-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models. (C) 2004 Elsevier Ltd. All rights reserved.