Methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)piperazin-1-yl]-5-oxo-2-propan-2-ylpentanoate | 1332895-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)piperazin-1-yl]-5-oxo-2-propan-2-ylpentanoate
• 英文别名: methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)piperazin-1-yl]-5-oxo-2-propan-2-ylpentanoate
• CAS: 1332895-69-8
• 化学式: C₂₆H₃₃BrN₂O₄
• 分子量: 517.463
• InChiKey: DYXWAEVVVRIZRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(4-溴苯基)-3-甲基丁酸甲酯 在 磺酰氯 、 18-冠醚-6 、 potassium tert-butylate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 Methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)piperazin-1-yl]-5-oxo-2-propan-2-ylpentanoate
  参考文献：
  名称：

  Successful reduction of off-target hERG toxicity by structural modification of a T-type calcium channel blocker

  摘要：

  To obtain an optimized T-type calcium channel blocker with reduced off-target hERG toxicity, we modified the structure of the original compound by introducing a zwitterion and reducing the basicity of the nitrogen. Among the structurally modified compounds we designed, compounds 5 and 6, which incorporate amides in place of the original compound's amines, most appreciably alleviated hERG toxicity while maintaining T-type calcium channel blocking activity. Notably, the benzimidazole amide 5 selectively blocked T-type calcium channels without inhibiting hERG (hERG/T-type >= 220) and L-type channels (L-type/T-type = 96), and exhibited an excellent pharmacokinetic profile in rats. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.078

文献信息

• Successful reduction of off-target hERG toxicity by structural modification of a T-type calcium channel blocker
  作者：Yeon Jae Choi、Jae Hong Seo、Kye Jung Shin

  DOI：10.1016/j.bmcl.2013.12.078

  日期：2014.2

  To obtain an optimized T-type calcium channel blocker with reduced off-target hERG toxicity, we modified the structure of the original compound by introducing a zwitterion and reducing the basicity of the nitrogen. Among the structurally modified compounds we designed, compounds 5 and 6, which incorporate amides in place of the original compound's amines, most appreciably alleviated hERG toxicity while maintaining T-type calcium channel blocking activity. Notably, the benzimidazole amide 5 selectively blocked T-type calcium channels without inhibiting hERG (hERG/T-type >= 220) and L-type channels (L-type/T-type = 96), and exhibited an excellent pharmacokinetic profile in rats. (C) 2013 Elsevier Ltd. All rights reserved.