1-Methyl-2,6-bis[3-(4-methylphenoxy)propyl]pyridin-1-ium;trifluoromethanesulfonate | 1428798-47-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-Methyl-2,6-bis[3-(4-methylphenoxy)propyl]pyridin-1-ium;trifluoromethanesulfonate
• 英文别名: 1-methyl-2,6-bis[3-(4-methylphenoxy)propyl]pyridin-1-ium;trifluoromethanesulfonate
• CAS: 1428798-47-3
• 化学式: CF₃O₃S*C₂₆H₃₂NO₂
• 分子量: 539.616
• InChiKey: BPTULUFUAHQUHJ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  87.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对甲酚 在 copper(l) iodide 、 trans-bis(triphenylphosphine)palladium dichloride 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 20.0 ℃ 、250.0 kPa 条件下， 反应 0.5h， 生成 1-Methyl-2,6-bis[3-(4-methylphenoxy)propyl]pyridin-1-ium;trifluoromethanesulfonate
  参考文献：
  名称：

  Strategies To Reduce hERG K⁺Channel Blockade. Exploring Heteroaromaticity and Rigidity in Novel Pyridine Analogues of Dofetilide

  摘要：

  Drug-induced blockade of the human ether-a-go-go-related gene K+ channel (hERG) represents one of the major antitarget concerns in pharmaceutical industry. SAR studies of this ion channel have shed light on the structural requirements for hERG interaction but most importantly may reveal drug design principles to reduce hERG affinity. In the present study, a novel library of neutral and positively charged heteroaromatic derivatives of the class III antiarrhythmic agent dofetilide was synthesized and assessed for hERG affinity in radioligand binding and manual patch clamp assays. Structural modifications of the pyridine moiety, side chain, and peripheral aromatic moieties were evaluated, thereby revealing approaches for reducing hERG binding affinity. In particular, we found that the extra rigidity imposed close to the positively charged pyridine moiety can be very efficient in decreasing hERG affinity.

  DOI：

  10.1021/jm301564f