methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-2-propan-2-ylpentanoate | 1552303-61-3

• 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: methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-2-propan-2-ylpentanoate
• CAS: 1552303-61-3
• 化学式: C₂₇H₃₄BrNO₃
• 分子量: 500.476
• InChiKey: VJNSKFRRVHJJRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-Methoxyphenylmagnesium bromide 在 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-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.