N-ethyl-5-acetylvaleramide ethylene dithioketal | 168268-54-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫代缩醛
• 英文名称: N-ethyl-5-acetylvaleramide ethylene dithioketal
• 英文别名: N-ethyl-5-(2-methyl-1,3-dithiolan-2-yl)pentanamide
• CAS: 168268-54-0
• 化学式: C₁₁H₂₁NOS₂
• 分子量: 247.426
• InChiKey: XVWZJTVVQCGHEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-ethyl-5-acetylvaleramide ethylene dithioketal 在 lithium aluminium tetrahydride 、 1,3-二溴-5,5-二甲基海因 、 氟化氢吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.42h， 生成 N-[4-[4-[(6,6-Difluoroheptyl)ethylamino]-1-hydroxybutyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential

  摘要：

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

  DOI：

  10.1021/jm0004289
• 作为产物：
  描述：

  5-乙酰基戊酸 在 boron trifluoride diacetate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 N-ethyl-5-acetylvaleramide ethylene dithioketal
  参考文献：
  名称：

  Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential

  摘要：

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

  DOI：

  10.1021/jm0004289

文献信息

• Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential
  作者：Jackson B. Hester、John K. Gibson、Lewis V. Buchanan、Madeline G. Cimini、Michael A. Clark、D. Edward Emmert、Michael A. Glavanovich、Rick J. Imbordino、Richelle J. LeMay、Moses W. McMillan、Salvatore C. Perricone、Donald M. Squires、Rodney R. Walters

  DOI：10.1021/jm0004289

  日期：2001.3.1

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.