4-硝基苯乙胺氢溴酸盐 | 69447-84-3

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 烃类硝化物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-硝基苯乙胺氢溴酸盐
• 中文别名: 对硝基苯乙胺氢溴酸盐；4-硝基-苯乙胺氢溴酸盐(简称:苯乙胺氢溴酸盐)；4-硝基苯乙基胺氢溴酸盐；4-硝基-β-苯乙胺氢溴酸盐
• 英文名称: p-nitrophenethylamine hydrobromide
• 英文别名: 4-nitro-phenethylamine; hydrobromide；4-Nitro-phenaethylamin; Hydrobromid；4-Nitrophenylethylamine hydrobromide；2-(4-nitrophenyl)ethanamine;hydrobromide
• CAS: 69447-84-3
• 化学式: BrH*C₈H₁₀N₂O₂
• mdl: MFCD07787604
• 分子量: 247.092
• InChiKey: IXEDXMYYHOYVRD-UHFFFAOYSA-N

物化性质

• 熔点：
  218 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.33
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  71.8
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2921499090
• 储存条件：
  存放条件：室温且干燥环境中

制备方法与用途

用途

4-硝基苯乙胺氢溴酸盐用作医药中间体，主要用于合成多菲利特。

反应信息

• 作为反应物：
  描述：

  4-硝基苯乙胺氢溴酸盐 在 盐酸 、 甲酸 、 铁粉 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 多非利特
  参考文献：
  名称：

  对甲基磺酰胺基苯乙胺类似物的计算机辅助设计，合成和生物学分析。

  摘要：

  III类抗心律不齐药物选择性地延迟了有效不应期（ERP），并增加了跨膜动作电位持续时间（APD）。根据我们以前的研究，通过CoMFA和CoMSIA的3D-QSAR技术研究了17种甲磺酰胺基苯乙胺类似物。3D-QSAR模型具有良好的预测能力，可以描述受体位点识别力的空间，静电和疏水性要求。根据此3D-QSAR分析提供的线索，我们设计并合成了一系列新的甲磺酰胺基苯乙胺（VIa-i）类似物。药理分析表明，这些新化合物的功能性不应期（FRP）延迟10毫秒的有效浓度与3D-QSAR预测值具有良好的相关性。值得注意的是，在化合物VIc的microM中，延迟FRP的最大变化百分比远高于多芬替利。结果表明3D-QSAR模型是可靠的。

  DOI：

  10.1016/s0960-894x(00)00412-1
• 作为产物：
  描述：

  N-(2-苯乙基)乙酰胺 在 硫酸 、 硝酸 作用下， 反应 8.0h， 生成 4-硝基苯乙胺氢溴酸盐
  参考文献：
  名称：

  New p-Methylsulfonamido Phenylethylamine Analogues as Class III Antiarrhythmic Agents:  Design, Synthesis, Biological Assay, and 3D-QSAR Analysis

  摘要：

  Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Using dofetilide (2) as a template of class III antiarrhythmic agents, we designed and synthesized 16 methylsulfonamido phenylethylamine analogues (4a-d and 5a-1). Pharmacological assay indicated that all of these compounds showed activity for increasing the ERP in isolated animal atrium; among them, the effective concentration of compound 4a is 1.6 x 10(-8) mol/L in increasing ERP by 10 ms, slightly less potent than that of 2, 1.1 x 10(-8) mol/L. Compound 4a also produced a slightly lower change in ERP at 10(-5) M, DeltaERP% = 17.5% (DeltaERP% = 24.0% for dofetilide). On the basis of this bioassay result, these 16 compounds together with dofetilide were investigated by the three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques of comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and the hologram QSAR (HQSAR). The 3D-QSAR models were tested with another 11 compounds (4e-h and 5m-s) that we synthesized later. Results revealed that the CoMFA, CoMSIA, and HQSAR predicted activities for the 11 newly synthesized compounds that have a good correlation with their experimental value, r(2) = 0.943, 0.891, and 0.809 for the three QSAR models, respectively. This indicates that the 3D-QSAR models proved a good predictive ability and could describe the steric, electrostatic, and hydrophobic requirements for recognition forces of the receptor site. On the basis of these results, we designed and synthesized another eight new analogues of methanesulfonamido phenylethyamine (6a-h) according to the clues provided by the 3D-QSAR analyses. Pharmacological assay indicated that the effective concentrations of delaying the ERP by 10 ins of these newly designed compounds correlated well with the 3D-QSAR predicted values. It is remarkable that the percent change of delaying ERP at 10-5 M compound 6c is much higher than that of dofetilide; the effective concentration of compound 6c is 5.0 x 10(-8)mol/L in increasing the ERP by 10 Ms, which is slightly lower than that of 2. The results showed that the 3D-QSAR models are reliable and can be extended to design new antiarrhythmic agents.

  DOI：

  10.1021/jm010574u

文献信息

• Microwave-assisted synthesis of primary amine HX salts from halides and 7 M ammonia in methanol
  作者：Mark G. Saulnier、Kurt Zimmermann、Charles P. Struzynski、Xiaopeng Sang、Upender Velaparthi、Mark Wittman、David B. Frennesson

  DOI：10.1016/j.tetlet.2003.10.146

  日期：2004.1

  on a variety of alkyl halides, as well as mesylates and tosylates. Benzylamines are obtained from benzyl halides without significant amounts of the secondary amine side products that result without microwave heating. Direct isolation of even highly volatile primary amines as their hydrogen halide salts makes the method ideal for use in parallel synthesis.

  直接从相应的卤化物进行的伯胺卤化氢盐的原子经济合成避免了产生大量的仲胺副产物，并且仅需蒸发溶剂即可获得产物，产率通常大于90％。该程序在130°C下于7 M氨的甲醇溶液（Aldrich）中进行0.5至2.5 h的微波辐射，并处理多种烷基卤化物，甲磺酸酯和甲苯磺酸酯。从苄基卤化物获得苄胺，而没有大量的仲胺副产物，而无需微波加热即可得到。直接分离高挥发性的伯胺作为卤化氢盐，使得该方法非常适合用于平行合成。
• US4278748A
  申请人：——

  公开号：US4278748A

  公开（公告）日：1981-07-14
• Computer-aided design, synthesis and biological assay of p-methylsulfonamido phenylethylamine analogues
  作者：Hong Liu、Min Ji、Hualiang Jiang、Ligang Liu、Weiyi Hua、Kaixian Chen、Ruyun Ji

  DOI：10.1016/s0960-894x(00)00412-1

  日期：2000.10

  hydrophobic requirements for recognition forces of the receptor site. According to the clues provided by this 3D-QSAR analysis, we designed and synthesized a series of new analogues of methanesulfonamido phenylethylamine (VIa-i). Pharmacological assay indicated that the effective concentrations of delaying the functional refractory period (FRP) 10ms of these new compounds have a good correlation with

  III类抗心律不齐药物选择性地延迟了有效不应期（ERP），并增加了跨膜动作电位持续时间（APD）。根据我们以前的研究，通过CoMFA和CoMSIA的3D-QSAR技术研究了17种甲磺酰胺基苯乙胺类似物。3D-QSAR模型具有良好的预测能力，可以描述受体位点识别力的空间，静电和疏水性要求。根据此3D-QSAR分析提供的线索，我们设计并合成了一系列新的甲磺酰胺基苯乙胺（VIa-i）类似物。药理分析表明，这些新化合物的功能性不应期（FRP）延迟10毫秒的有效浓度与3D-QSAR预测值具有良好的相关性。值得注意的是，在化合物VIc的microM中，延迟FRP的最大变化百分比远高于多芬替利。结果表明3D-QSAR模型是可靠的。
• New <i>p</i>-Methylsulfonamido Phenylethylamine Analogues as Class III Antiarrhythmic Agents:  Design, Synthesis, Biological Assay, and 3D-QSAR Analysis
  作者：Hong Liu、Ming Ji、Xiaomin Luo、Jianhua Shen、Xiaoqin Huang、Weiyi Hua、Hualiang Jiang、Kaixian Chen

  DOI：10.1021/jm010574u

  日期：2002.7.1

  Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Using dofetilide (2) as a template of class III antiarrhythmic agents, we designed and synthesized 16 methylsulfonamido phenylethylamine analogues (4a-d and 5a-1). Pharmacological assay indicated that all of these compounds showed activity for increasing the ERP in isolated animal atrium; among them, the effective concentration of compound 4a is 1.6 x 10(-8) mol/L in increasing ERP by 10 ms, slightly less potent than that of 2, 1.1 x 10(-8) mol/L. Compound 4a also produced a slightly lower change in ERP at 10(-5) M, DeltaERP% = 17.5% (DeltaERP% = 24.0% for dofetilide). On the basis of this bioassay result, these 16 compounds together with dofetilide were investigated by the three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques of comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and the hologram QSAR (HQSAR). The 3D-QSAR models were tested with another 11 compounds (4e-h and 5m-s) that we synthesized later. Results revealed that the CoMFA, CoMSIA, and HQSAR predicted activities for the 11 newly synthesized compounds that have a good correlation with their experimental value, r(2) = 0.943, 0.891, and 0.809 for the three QSAR models, respectively. This indicates that the 3D-QSAR models proved a good predictive ability and could describe the steric, electrostatic, and hydrophobic requirements for recognition forces of the receptor site. On the basis of these results, we designed and synthesized another eight new analogues of methanesulfonamido phenylethyamine (6a-h) according to the clues provided by the 3D-QSAR analyses. Pharmacological assay indicated that the effective concentrations of delaying the ERP by 10 ins of these newly designed compounds correlated well with the 3D-QSAR predicted values. It is remarkable that the percent change of delaying ERP at 10-5 M compound 6c is much higher than that of dofetilide; the effective concentration of compound 6c is 5.0 x 10(-8)mol/L in increasing the ERP by 10 Ms, which is slightly lower than that of 2. The results showed that the 3D-QSAR models are reliable and can be extended to design new antiarrhythmic agents.