(1-(2-hydroxy-3-(4-phenylpiperazin-1-yl)-propyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)acetic acid methyl ester hydrochloride | 1370333-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (1-(2-hydroxy-3-(4-phenylpiperazin-1-yl)-propyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)acetic acid methyl ester hydrochloride
• 英文别名: Methyl 2-[3-[2-hydroxy-3-(4-phenylpiperazin-1-yl)propyl]-2,5-dioxo-4,4-diphenylimidazolidin-1-yl]acetate;hydrochloride
• CAS: 1370333-44-0
• 化学式: C₃₁H₃₄N₄O₅*ClH
• 分子量: 579.096
• InChiKey: RDWPUEIUIZHMJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  93.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (1-(2-hydroxy-3-(4-phenylpiperazin-1-yl)-propyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)acetic acid methyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 以94%的产率得到(1-(2-hydroxy-3-(4-phenylpiperazin-1-yl)-propyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)acetic acid methyl ester hydrochloride
  参考文献：
  名称：

  Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α1-adrenoceptor affinities

  摘要：

  An association between alpha(1)-adrenoceptor affinities, hERG K+-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a-21a) was investigated. New compounds were synthesized and tested for their affinity for alpha(1)-adrenoceptors in radioligand binding assay using [H-3]-prazosin as a selective radioligand. Antiarrhythmic activities in adrenaline-and barium chloride-induced arrhythmia models, an influence of the phenylpiperazine derivatives on the ECG-components and blood pressure were tested in vivo in normotensive rats. The hERG K+-antagonistic properties of the most potent antiarrhythmic agents were investigated in silico by the use of program QikProp. The highest alpha(1)-adrenoceptor affinity (K-i = 4.7 nM) and the strongest antiarrhythmic activity in adrenaline induced arrhythmia (ED50 = 0.1 mg/kg) was found for 1-(4-(4-(2-methoxyphenyl)piperazin-1-yl) butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione hydrochloride (19a). The results indicated a significant correlation between alpha(1)-AR affinities (pK(i)) and antiarrhythmic activity (ED50) in adrenaline model (R-2 = 0.92, p < 0.005). Influence of the examined phenylpiperazine hydantoin derivatives on hERG K+ channel, predicted by means of in silico methods, suggested their hERG K+-blocking properties. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.009