N-<2-(dimethylamino)ethyl>-3-methyl-4-nitrobenzamide | 112740-71-3

• 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-<2-(dimethylamino)ethyl>-3-methyl-4-nitrobenzamide
• 英文别名: N-[2-(diethylamino)ethyl]-3-methyl-4-nitrobenzamide
• CAS: 112740-71-3
• 化学式: C₁₄H₂₁N₃O₃
• 分子量: 279.339
• InChiKey: QACMJRBWNQFKKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-<2-(dimethylamino)ethyl>-3-methyl-4-nitrobenzamide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 生成 4-amino-N-[2-(dimethylamino)ethyl]-3-methylbenzamide
  参考文献：
  名称：

  Electrophysiologic and antiarrhythmic activities of 4-amino-N-[2-(diethylamino)ethyl]-3,5-dimethylbenzamide, a sterically hindered procainamide analog

  摘要：

  Procainamide is a widely used antiarrhythmic that is fraught with therapeutic limitations such as a short half-life, production of autoimmune antibodies and a lupus-like syndrome, and complex pharmacokinetics. We synthesized the congeners of procainamide possessing one or two methyl substituents ortho to the 4-amino moiety (compounds 4 and 5, respectively), in order to sterically encumber the 4-amino substituent and prevent or diminish the rate of metabolic N-acetylation. Moreover, we anticipated that this structural alteration might eliminate the autoimmune toxicities associated with procainamide. Like procainamide, the two methylated analogues significantly reduced the rate of rise and amplitude of the action potential when studied in isolated canine Purkinje fibers. Whereas procainamide caused no significant change in action potential duration (APD), both methylated congeners significantly reduced APD at 70% and 95% repolarization. Moreover, the dimethylated congener was significantly more efficacious than procainamide in reducing ERP (effective refractory period) and increasing the ERP/APD70. The ability of these compounds to block ouabain-induced arrhythmias was studied in anesthetized dogs. Addition of two methyl groups ortho to the amine produced an increase in potency: The conversion doses for procainamide and the monomethyl and dimethyl congeners were 19.0, 18.3, and 14.3 mg/kg, respectively, following iv administration. After iv administration to rats, procainamide was extensively metabolized to N-acetylprocainamide and displayed a half-life of 0.4 h. In contrast, dimethylprocainamide was not metabolized by N-acetylation, had a half-life of 1.4 h, and provided greater peak plasma concentrations. Thus, addition of methyl substituents ortho to the 4-amino group of procainamide alters the electrophysiological characteristics of the compound, increases its potency against ouabain-induced arrhythmias in vivo, increases its plasma half-life, and prevents N-acetylation.

  DOI：

  10.1021/jm00402a006
• 作为产物：
  描述：

  N,N-二乙基乙二胺 生成 N-<2-(dimethylamino)ethyl>-3-methyl-4-nitrobenzamide
  参考文献：
  名称：

  ROBERTSON, DAVID W.;BEEDLE, E. E.;WILSON, HARVE;JOHN, PARLI C.;SMALLWOOD,+, J. MED. CHEM., 31,(1988) N 7, 1290-1295

  摘要：

  DOI：

文献信息

• ROBERTSON, DAVID W.;BEEDLE, E. E.;WILSON, HARVE;JOHN, PARLI C.;SMALLWOOD,+, J. MED. CHEM., 31,(1988) N 7, 1290-1295
  作者：ROBERTSON, DAVID W.、BEEDLE, E. E.、WILSON, HARVE、JOHN, PARLI C.、SMALLWOOD,+

  DOI：——

  日期：——
• Electrophysiologic and antiarrhythmic activities of 4-amino-N-[2-(diethylamino)ethyl]-3,5-dimethylbenzamide, a sterically hindered procainamide analog
  作者：David W. Robertson、E. E. Beedle、Harve Wilson、C. John Parli、Jeffrey K. Smallwood、Mitchell I. Steinberg

  DOI：10.1021/jm00402a006

  日期：1988.7

  Procainamide is a widely used antiarrhythmic that is fraught with therapeutic limitations such as a short half-life, production of autoimmune antibodies and a lupus-like syndrome, and complex pharmacokinetics. We synthesized the congeners of procainamide possessing one or two methyl substituents ortho to the 4-amino moiety (compounds 4 and 5, respectively), in order to sterically encumber the 4-amino substituent and prevent or diminish the rate of metabolic N-acetylation. Moreover, we anticipated that this structural alteration might eliminate the autoimmune toxicities associated with procainamide. Like procainamide, the two methylated analogues significantly reduced the rate of rise and amplitude of the action potential when studied in isolated canine Purkinje fibers. Whereas procainamide caused no significant change in action potential duration (APD), both methylated congeners significantly reduced APD at 70% and 95% repolarization. Moreover, the dimethylated congener was significantly more efficacious than procainamide in reducing ERP (effective refractory period) and increasing the ERP/APD70. The ability of these compounds to block ouabain-induced arrhythmias was studied in anesthetized dogs. Addition of two methyl groups ortho to the amine produced an increase in potency: The conversion doses for procainamide and the monomethyl and dimethyl congeners were 19.0, 18.3, and 14.3 mg/kg, respectively, following iv administration. After iv administration to rats, procainamide was extensively metabolized to N-acetylprocainamide and displayed a half-life of 0.4 h. In contrast, dimethylprocainamide was not metabolized by N-acetylation, had a half-life of 1.4 h, and provided greater peak plasma concentrations. Thus, addition of methyl substituents ortho to the 4-amino group of procainamide alters the electrophysiological characteristics of the compound, increases its potency against ouabain-induced arrhythmias in vivo, increases its plasma half-life, and prevents N-acetylation.