N-[4-[2-[benzyl-[2-[4-(methanesulfonamido)phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide | 226992-16-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[4-[2-[benzyl-[2-[4-(methanesulfonamido)phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide
• CAS: 226992-16-1
• 化学式: C₂₅H₃₁N₃O₅S₂
• 分子量: 517.67
• InChiKey: ANHBBRKNCYZBJB-UHFFFAOYSA-N

物化性质

• 沸点：
  680.4±65.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[4-[2-[benzyl-[2-[4-(methanesulfonamido)phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 反应 8.0h， 以41.8%的产率得到N-去甲基多非利特
  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
• 作为产物：
  描述：

  N-[4-[2-[2-(4-nitrophenyl)ethylamino]ethoxy]phenyl]methanesulfonamide 在 盐酸 、 铁粉 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-[4-[2-[benzyl-[2-[4-(methanesulfonamido)phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide
  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

文献信息

• 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.