2-(diethylamino)ethyl (2R)-2-(naphthalen-1-ylmethyl)-3-[(2R)-oxolan-2-yl]propanoate;oxalic acid | 3200-06-4

• 物质功能分类: 原料药 - 循环系统用药 - 周围血管扩张药
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(diethylamino)ethyl (2R)-2-(naphthalen-1-ylmethyl)-3-[(2R)-oxolan-2-yl]propanoate;oxalic acid
• CAS: 3200-06-4；4825-57-4；29038-64-0；86258-36-8；86258-39-1；139240-24-7；139240-25-8；139240-26-9；139270-29-4
• 化学式: C₂H₂O₄*C₂₄H₃₃NO₃
• 分子量: 473.566
• InChiKey: SSAJNPNVUYMUCI-HLUKFBSCSA-N

物化性质

• 熔点：
  110-111°
• 沸点：
  574°C (rough estimate)
• 密度：
  1.2205 (rough estimate)
• 溶解度：
  易溶于水，易溶于或溶于乙醇（96%），微溶于或微溶于丙酮。

计算性质

• 辛醇/水分配系数(LogP)：
  3.61
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• 危险品标志：
  Xn,Xi
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  29321900

制备方法与用途

概述

萘呋胺酯草酸盐是一种有机酸物质，作为脑血管和外周血管的扩张剂，它能够拮抗5-羟色胺及缓激肽的作用。该药物还能使细胞内ATP增多，从而改善细胞代谢；降低血液及血浆粘稠度与纤维蛋白原浓度；增加细胞的氧化能力并对细胞缺氧具有保护作用；此外还表现出罂粟碱样的解痉效果，缓慢而持久。

药理作用

萘呋胺酯草酸盐主要用于治疗心脑血管和周围血管疾病。其扩张作用比烟酸更强，并且增强脑血管流量的作用较罂粟更为缓慢而持久。据认为，它的临床应用比罂粟碱更安全，对严重下肢动脉炎的疗效显著且迅速。

应用

萘呋胺酯草酸盐同样适用于治疗心脑血管与周围血管疾病。其扩张作用强于烟酸，并且增强脑血管流量的作用较罂粟更为缓慢而持久。

生物活性

Naftidrofuryl oxalate（又称Nafronyl oxalate salt）是一种用于管理外周血和脑血管病症如血管扩张药的药物。它增加细胞氧化能力，同时也是5-HT2受体拮抗剂。

靶点

Target	Value
5-HT2 receptor	()

体外研究

Naftidrofuryl oxalate（Nafronyl oxalate salt）可能有效缓解肌肉痉挛疼痛。在治疗周围动脉疾病(PAD)方面，它是唯一一种被认为成本效益较高的血管活性药物。

此外，Naftidrofuryl oxalate（Nafronyl oxalate salt）在最大行走距离(MWD)和无痛行走距离(PFWD)两项指标中均排名第一（概率分别为0.947和0.987），其次是西洛他唑和普利多菲林。该药物对间歇性跛行的治疗效果显著，且不良事件较少。

反应信息

• 作为产物：
  描述：

  (naphthalen-1-ylmethyl)[(2R)-tetrahydrofuran-2-ylmethyl]malonic 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 2.5h， 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

文献信息

• 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.