2-(2-(3-aminopropylamino)ethylamino)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)ethanol | 1258387-05-1

• 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: 2-(2-(3-aminopropylamino)ethylamino)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)ethanol
• 英文别名: WR 308384；2-[2-(3-Aminopropylamino)ethylamino]-1-[2,8-bis(trifluoromethyl)quinolin-4-yl]ethanol
• CAS: 1258387-05-1
• 化学式: C₁₈H₂₂F₆N₄O
• 分子量: 424.389
• InChiKey: HWTJCQFESOMBLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.2
• 氢给体数：
  4
• 氢受体数：
  11

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 2-(2-(3-aminopropylamino)ethylamino)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)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

文献信息

• [EN] NEXT GENERATION QUINOLOINE METHANOLS<br/>[FR] QUINOLÉINE MÉTHANOLS DE NOUVELLE GÉNÉRATION
  申请人：US OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE ARMY ON BEHALF OF U S

  公开号：WO2010144101A1

  公开（公告）日：2010-12-16

  The present invention relates to new quinoline methanol derivatives and therapeutic compostions comprising one or more quinoline methanol derivatives. These compositons are useful in the reduction, treatment, or prevention of malaria, microbial, parasitic, protozoan, bacterial, and fungal diseases and conditions. Advantageously, compositions of the invention are less able to cross the blood-brain barrier than mefloquine and as a result produce fewer adverse side effects to the central nervous system as compared to mefloquine.
• [EN] PENTAFLUOROSULFANYL ANALOGS OF MEFLOQUINE<br/>[FR] ANALOGUES DE PENTAFLUOROSULFANYLE DE LA MÉFLOQUINE
  申请人：US OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE ARMY ON BEHALF OF U S ARMY MEDICAL RES AND MATE

  公开号：WO2010144102A1

  公开（公告）日：2010-12-16

  The present invention relates to new mefloquine derivatives and therapeutic compositions comprising one or more mefloquine derivatives. Mefloquine derivatives of the invention have at least one pentafluorosulfanyl moiety substitution at the 6 or 7 or 8 position. Certain mefloquine derivatives further include a quinoline methonal moiety substitution at the 4 position. These compositions are useful in the reduction, treatment, or prevention of malaria, microbial, parasitic, protozoan, bacterial, and fungal diseases and conditions. Advantageously, compositions of the invention are less able to cross the blood-brain barrier than mefloquine and as a result produce fewer adverse side effects to the central nervous system as compared to mefloquine.
• Structure–Activity Relationships of 4-Position Diamine Quinoline Methanols as Intermittent Preventative Treatment (IPT) against <i>Plasmodium falciparum</i>
  作者：Erin Milner、Sean Gardner、Jay Moon、Kristina Grauer、Jennifer Auschwitz、Ian Bathurst、Diana Caridha、Lucia Gerena、Montip Gettayacamin、Jacob Johnson、Michael Kozar、Patricia Lee、Susan Leed、Qigui Li、William McCalmont、Victor Melendez、Norma Roncal、Richard Sciotti、Bryan Smith、Jason Sousa、Anchalee Tungtaeng、Peter Wipf、Geoffrey Dow

  DOI：10.1021/jm200647u

  日期：2011.9.22

  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.