N-(4-(4-chlorophenoxy)but-2-yn-1-yl)-N-ethylheptan-1-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(4-(4-chlorophenoxy)but-2-yn-1-yl)-N-ethylheptan-1-amine
• 英文别名: N-[4-(4-chlorophenoxy)but-2-ynyl]-N-ethylheptan-1-amine
• 化学式: C₁₉H₂₈ClNO
• 分子量: 321.89
• InChiKey: OAAXUVBOELLOHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对氯苯酚 在 copper(II) acetate monohydrate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 丙酮 、 甲苯 为溶剂， 反应 27.0h， 生成 N-(4-(4-chlorophenoxy)but-2-yn-1-yl)-N-ethylheptan-1-amine
  参考文献：
  名称：

  Removal of Human Ether-à-go-go Related Gene (hERG) K⁺ Channel Affinity through Rigidity: A Case of Clofilium Analogues

  摘要：

  Cardiotoxicity is a side effect that plagues modern drug design and is very often due to the off-target blockade of the human ether-a-go-go related gene (hERG) potassium channel. To better understand the structural determinants of this blockade, we designed and synthesized a series of 40 derivatives of clofilium, a class III antiarrhythrnic agent. These were evaluated in radioligand binding and patch-damp assays to establish structure affinity relationships (SAR) for this potassium channel. Efforts were especially focused on studying the influence of the structural rigidity and the nature of the linkers composing the clofilium scaffold. It was shown that introducing triple bonds and oxygen atoms in the n-butyl linker of the molecule greatly reduced affinity without significantly modifying the pK(a) of the essential basic nitrogen. These findings could prove useful in the first stages of drug discovery as a systematic way of reducing the risk of hERG K+ channel blockade-induced cardiotoxicity.

  DOI：

  10.1021/jm4010434

文献信息

• Removal of Human Ether-à-go-go Related Gene (hERG) K⁺ Channel Affinity through Rigidity: A Case of Clofilium Analogues
  作者：Julien Louvel、João F. S. Carvalho、Zhiyi Yu、Marjolein Soethoudt、Eelke B. Lenselink、Elisabeth Klaasse、Johannes Brussee、Adriaan P. IJzerman

  DOI：10.1021/jm4010434

  日期：2013.12.12

  Cardiotoxicity is a side effect that plagues modern drug design and is very often due to the off-target blockade of the human ether-a-go-go related gene (hERG) potassium channel. To better understand the structural determinants of this blockade, we designed and synthesized a series of 40 derivatives of clofilium, a class III antiarrhythrnic agent. These were evaluated in radioligand binding and patch-damp assays to establish structure affinity relationships (SAR) for this potassium channel. Efforts were especially focused on studying the influence of the structural rigidity and the nature of the linkers composing the clofilium scaffold. It was shown that introducing triple bonds and oxygen atoms in the n-butyl linker of the molecule greatly reduced affinity without significantly modifying the pK(a) of the essential basic nitrogen. These findings could prove useful in the first stages of drug discovery as a systematic way of reducing the risk of hERG K+ channel blockade-induced cardiotoxicity.