2-[(naphthalen-1-yl)methyl]-3-[(R)-tetrahydrofuran-2-yl]propanoic acid | 1392400-79-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[(naphthalen-1-yl)methyl]-3-[(R)-tetrahydrofuran-2-yl]propanoic acid
• 英文别名: 2-(naphthalen-1-ylmethyl)-3-[(2R)-oxolan-2-yl]propanoic acid
• CAS: 1392400-79-1
• 化学式: C₁₈H₂₀O₃
• 分子量: 284.355
• InChiKey: VEJYFDMNWGFBCT-OEMAIJDKSA-N

物化性质

• 沸点：
  464.2±20.0 °C(Predicted)
• 密度：
  1.183±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(naphthalen-1-yl)methyl]-3-[(R)-tetrahydrofuran-2-yl]propanoic acid 在 R(+)-alpha-甲基苄胺 、 potassium carbonate 作用下， 以 乙醚 、 水 、 丙酮 、 甲苯 为溶剂， 反应 1.5h， 生成 2-(diethylamino)ethyl (2R)-2-(naphthalen-1-ylmethyl)-3-[(2R)-oxolan-2-yl]propanoate;oxalic acid
  参考文献：
  名称：

  Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor

  摘要：

  Naftidrofuryl oxalate (Praxilene (R), 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (2-HT2) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT2A receptor, and the C-2' configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT2A receptor that have clinical significance as vasodilators and CNS agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.093
• 作为产物：
  描述：

  (氯甲基)萘 在 sodium hydride 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-[(naphthalen-1-yl)methyl]-3-[(R)-tetrahydrofuran-2-yl]propanoic acid
  参考文献：
  名称：

  Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor

  摘要：

  Naftidrofuryl oxalate (Praxilene (R), 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (2-HT2) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT2A receptor, and the C-2' configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT2A receptor that have clinical significance as vasodilators and CNS agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.093

文献信息

• [EN] COMBINATION OF PICOTAMIDE WITH NAFRONYL<br/>[FR] COMBINAISON DE PICOTAMIDE AVEC DU NAFRONYL
  申请人：DYBLY AG

  公开号：WO2009000907A2

  公开（公告）日：2008-12-31

  [EN] The invention relates to a combination of picotamide (N,N'-bis-(3-picolyl)-4-methoxy- isophthalamide) and nafronyl (2-diethylaminoethyl 2-(naphthalen-1-ylmethyl)-3-(oxolan-2-yl)propanoate), pharmaceutical compositions, and use of this combination in the treatment of intermittent claudication.
  [FR] L'invention porte sur une combinaison de picotamide (N,N'-bis-(3-picolyl)-4-méthoxy-isophtalamide) et de nafronyl(2-(naphtalèn-1-ylméthyl)-3-(oxolan-2-yl)propanoate de 2-diéthylaminoéthyle), sur des compositions pharmaceutiques et sur l'utilisation de cette combinaison dans le traitement de la claudication intermittente.
• Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor
  作者：Jia Hao、Bo Chen、Yiwu Yao、Murad Hossain、Takafumi Nagatomo、Hequan Yao、Lingyi Kong、Hongbin Sun

  DOI：10.1016/j.bmcl.2012.03.093

  日期：2012.5

  Naftidrofuryl oxalate (Praxilene (R), 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (2-HT2) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT2A receptor, and the C-2' configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT2A receptor that have clinical significance as vasodilators and CNS agents. (C) 2012 Elsevier Ltd. All rights reserved.