(1R,9aR)-1-[(2,6-dimethyl-4-nitrophenoxy)methyl]-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizine | 927267-35-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: (1R,9aR)-1-[(2,6-dimethyl-4-nitrophenoxy)methyl]-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizine
• CAS: 927267-35-4
• 化学式: C₁₈H₂₆N₂O₃
• 分子量: 318.416
• InChiKey: XBEJLDNYKPUPTI-DOTOQJQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,9aR)-1-[(2,6-dimethyl-4-nitrophenoxy)methyl]-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizine 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 以 乙醇 为溶剂， 反应 1.67h， 生成 N-[4-[[(1R,9aR)-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizin-1-yl]methoxy]-3,5-dimethylphenyl]methanesulfonamide
  参考文献：
  名称：

  Novel Quinolizidinyl Derivatives as Antiarrhythmic Agents

  摘要：

  Eighteen analogues of lidocaine, mexiletine, and procainamide were synthesized, replacing their aminoalkyl chains with the rigid and cumbersome quinolizidine nucleus. The target compounds were tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. Most compounds exhibited from moderate to high antiarrhythmic activity, and compounds 7, 9, and 19 were more active and potent than quinidine and lidocaine, while producing only modest inotropic, chronotropic, and vasorelaxant effects. These compounds were studied on spontaneously beating Langendorff-perfused gp heart. While quinidine and amiodarone produced a dose-dependent prolongation of all the ECG intervals, compounds 7, 9, and 19, even at concentrations 10-20 times higher than EC50 for the antiarrhythmic activity, only moderately prolonged the PR and QT intervals, leaving unchanged the QRS complex. Ether 7 deserves further investigations due to its interesting cardiovascular profile.

  DOI：

  10.1021/jm060878m
• 作为产物：
  描述：

  chlorolupinane 、 2,6-二甲基-4-硝基苯酚 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以48%的产率得到(1R,9aR)-1-[(2,6-dimethyl-4-nitrophenoxy)methyl]-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizine
  参考文献：
  名称：

  Novel Quinolizidinyl Derivatives as Antiarrhythmic Agents

  摘要：

  Eighteen analogues of lidocaine, mexiletine, and procainamide were synthesized, replacing their aminoalkyl chains with the rigid and cumbersome quinolizidine nucleus. The target compounds were tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. Most compounds exhibited from moderate to high antiarrhythmic activity, and compounds 7, 9, and 19 were more active and potent than quinidine and lidocaine, while producing only modest inotropic, chronotropic, and vasorelaxant effects. These compounds were studied on spontaneously beating Langendorff-perfused gp heart. While quinidine and amiodarone produced a dose-dependent prolongation of all the ECG intervals, compounds 7, 9, and 19, even at concentrations 10-20 times higher than EC50 for the antiarrhythmic activity, only moderately prolonged the PR and QT intervals, leaving unchanged the QRS complex. Ether 7 deserves further investigations due to its interesting cardiovascular profile.

  DOI：

  10.1021/jm060878m

文献信息

• Novel Quinolizidinyl Derivatives as Antiarrhythmic Agents
  作者：Iana Vazzana、Roberta Budriesi、Emanuela Terranova、Pierfranco Ioan、Maria Paola Ugenti、Bruno Tasso、Alberto Chiarini、Fabio Sparatore

  DOI：10.1021/jm060878m

  日期：2007.1.1

  Eighteen analogues of lidocaine, mexiletine, and procainamide were synthesized, replacing their aminoalkyl chains with the rigid and cumbersome quinolizidine nucleus. The target compounds were tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. Most compounds exhibited from moderate to high antiarrhythmic activity, and compounds 7, 9, and 19 were more active and potent than quinidine and lidocaine, while producing only modest inotropic, chronotropic, and vasorelaxant effects. These compounds were studied on spontaneously beating Langendorff-perfused gp heart. While quinidine and amiodarone produced a dose-dependent prolongation of all the ECG intervals, compounds 7, 9, and 19, even at concentrations 10-20 times higher than EC50 for the antiarrhythmic activity, only moderately prolonged the PR and QT intervals, leaving unchanged the QRS complex. Ether 7 deserves further investigations due to its interesting cardiovascular profile.