1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(((3aR,6aR)-octahydrocyclopenta[c]pyrrol-3a-yl)methylamino)ethanol | 1329673-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(((3aR,6aR)-octahydrocyclopenta[c]pyrrol-3a-yl)methylamino)ethanol
• 英文别名: WR 319577；2-[[(3aR,6aR)-2,3,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-3a-yl]methylamino]-1-[2,8-bis(trifluoromethyl)quinolin-4-yl]ethanol
• CAS: 1329673-68-8
• 化学式: C₂₁H₂₃F₆N₃O
• 分子量: 447.424
• InChiKey: VLOQWKOLWOGCDR-JFNNDOMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  57.2
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,8-双(三氟甲基)-4-羟基喹啉 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 potassium carbonate 、 间氯过氧苯甲酸 、 三溴氧磷 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.75h， 生成 1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(((3aR,6aR)-octahydrocyclopenta[c]pyrrol-3a-yl)methylamino)ethanol
  参考文献：
  名称：

  Structure–Activity Relationships of 4-Position Diamine Quinoline Methanols as Intermittent Preventative Treatment (IPT) against Plasmodium falciparum

  摘要：

  A library of diamine quinoline methanols were designed based on the mefloquine scaffold. The systematic variation of the 4-position amino alcohol side chain led to analogues that maintained potency while reducing accumulation in the central nervous system (CNS). Although the mechanism of action remains elusive, these data indicate that the 4-position side chain is critical for activity and that potency (as measured by IC(90)) does not correlate with accumulation in the CNS. A new lead compound, (S)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(2-(cyclopropylamino)ethylamino)ethanol (WR621308), was identified with single dose efficacy and substantially lower permeability across MDCK cell monolayers than mefloquine. This compound could be appropriate for intermittent preventative treatment (IPTx) indications or other malaria treatments currently approved for mefloquine.

  DOI：

  10.1021/jm200647u