2,8-bis(trifluoromethyl)-4-vinylquinoline | 1031928-53-6

• 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: 2,8-bis(trifluoromethyl)-4-vinylquinoline
• 英文别名: 4-ethenyl-2,8-bis(trifluoromethyl)quinoline
• CAS: 1031928-53-6
• 化学式: C₁₃H₇F₆N
• 分子量: 291.196
• InChiKey: WRQUOKZRJAVFGC-UHFFFAOYSA-N

物化性质

• 熔点：
  76 °C
• 沸点：
  288.0±35.0 °C(Predicted)
• 密度：
  1.388±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,8-bis(trifluoromethyl)-4-vinylquinoline 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 0.25h， 生成 2-(2-aminoethylamino)-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
• 作为产物：
  描述：

  2,8-双(三氟甲基)-4-羟基喹啉 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三溴氧磷 作用下， 生成 2,8-bis(trifluoromethyl)-4-vinylquinoline
  参考文献：
  名称：

  新型喹啉氨基乙醇类抗菌药物的合成与研究

  摘要：

  缺乏具有与耐药菌的传播有关的新颖作用方式的抗生素，使得与传染病的斗争特别具有挑战性。喹啉核心存在于几种抗感染药中，例如甲氟喹和苯达喹啉。这项工作设定了两个主要目标。首先，我们评估了先前的喹啉3的抗分枝杆菌特性，这些喹啉已被确认为抗ESKAPEE（粪肠球菌，金黄色葡萄球菌，肺炎克雷伯菌，鲍曼不动杆菌，铜绿假单胞菌，肠杆菌属和大肠杆菌）的良好候选者。其次，设计了一个新的系列4并针对相同的细菌菌株进行了评估，以一对3m / 3n对映异构体为首。通过五步不对称合成，以良好的对映体过量（> 90％）制备了二十多种化合物4。有趣的是，系列3的所有化合物对鸟分枝杆菌均​​有效，MIC = 2–16 µg / mL，而系列4的活性较低。系列3和4通常都比甲氟喹对ESKAPEE细菌更具活性。根据全球亲脂性，喹啉4对革兰氏阳性细菌（MIC≤4 µg / mL，4c–4h和4k / 4l）或大肠杆菌（MIC =

  DOI：

  10.3390/ph12020091

文献信息

• Synthesis and Study of New Quinolineaminoethanols as Anti-Bacterial Drugs
  作者：Laumaillé、Dassonville-Klimpt、Peltier、Mullié、Andréjak、Da-Nascimento、Castelain、Sonnet

  DOI：10.3390/ph12020091

  日期：——

  baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli) bacteria. Secondly, a new series 4 was designed and assessed against the same bacteria strains, taking the pair of enantiomers 3m/3n as the lead. More than twenty compounds 4 were prepared through a five-step asymmetric synthesis with good enantiomeric excesses (>90%). Interestingly, all compounds of series 3 were efficient on

  缺乏具有与耐药菌的传播有关的新颖作用方式的抗生素，使得与传染病的斗争特别具有挑战性。喹啉核心存在于几种抗感染药中，例如甲氟喹和苯达喹啉。这项工作设定了两个主要目标。首先，我们评估了先前的喹啉3的抗分枝杆菌特性，这些喹啉已被确认为抗ESKAPEE（粪肠球菌，金黄色葡萄球菌，肺炎克雷伯菌，鲍曼不动杆菌，铜绿假单胞菌，肠杆菌属和大肠杆菌）的良好候选者。其次，设计了一个新的系列4并针对相同的细菌菌株进行了评估，以一对3m / 3n对映异构体为首。通过五步不对称合成，以良好的对映体过量（> 90％）制备了二十多种化合物4。有趣的是，系列3的所有化合物对鸟分枝杆菌均​​有效，MIC = 2–16 µg / mL，而系列4的活性较低。系列3和4通常都比甲氟喹对ESKAPEE细菌更具活性。根据全球亲脂性，喹啉4对革兰氏阳性细菌（MIC≤4 µg / mL，4c–4h和4k / 4l）或大肠杆菌（MIC =
• 一种2,8-双(三氟甲基)-4-羟基喹啉衍生物在制备和防治农业病害中的用途
  申请人：兰州大学

  公开号：CN112608275A

  公开（公告）日：2021-04-06

  本发明公开了一种2,8‑双(三氟甲基)‑4‑羟基喹啉衍生物在制备和防治农业病害中的用途。活性测试结果表明，本发明所述化合物对油菜菌核病菌、番茄灰霉病菌、小麦赤霉病菌和立枯丝核病菌四种植物病源真菌表现出潜在的抑制活性，可作为杀菌剂来开发。
• Enantioselective synthesis method of 4-aminoalcoholquinoline derivatives and the use
  申请人：Université de Picardie Jules Verne

  公开号：EP2487157A1

  公开（公告）日：2012-08-15

  Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (-)-enantiomer. Moreover, the (-)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemate 4-aminoalcoholquinolines showed interesting anti-malarial activities. Herein, the present invention describes an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcoholquinoline derivatives through the 4-oxirane key-intermediate. A regioselective SN2 ring opening of this epoxide, by diverse amines, allows to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcoholquinoline derivatives.

  梅氟喹诺酮衍生物与氯喹诺酮衍生物相比，迄今为止尚未广泛研究。因此，梅氟喹诺酮及其衍生物仍然是非常有吸引力的合成目标。虽然梅氟喹诺酮通常作为外消旋混合物在临床上使用，但一些研究表明其（+）-对映体比（-）-对映体更有效。此外，（-）-对映体由于与中枢神经系统腺苷受体的反应而导致副作用，而（+）-对映体则不会在该结合位点结合。最近，不同的外消旋4-氨基醇喹啉库显示出有趣的抗疟活性。在此，本发明描述了一种对映纯的合成和直接的途径，通过4-环氧丙烷关键中间体制备纯对映体4-氨基醇喹啉衍生物。通过多种胺的区域选择性SN2环开放该环氧化物，可以获得相应的（R）或（S）4-氨基喹啉，并且收率和对映体过量通常高于92％。所报告的方法适用于合成大量对映纯的4-氨基醇喹啉衍生物。
• [EN] 4-AMINOALCOHOLQUINOLINE DERIVATIVES, ENANTIOSELECTIVE SYNTHESIS METHODS AND THE USE THEREOF<br/>[FR] DÉRIVÉS DE 4-AMINO-ALCOOLQUINOLÉINE, PROCÉDÉS DE SYNTHÈSE ÉNANTIOSÉLECTIVE ET UTILISATION DE CEUX-CI
  申请人：UNIV PICARDIE

  公开号：WO2012107532A1

  公开（公告）日：2012-08-16

  The present invention is intended to provide new antimalarial compounds with a strong antimalarial activity as well as antibacterial activity with few neurological side effects and a new enantioselective pathway to mefloquine amino-analogs allowing the access of such compounds. The present invention relates to new 4 -aminoalcohol quinoline derivatives of formula (I), as well as the synthesis methods and the uses of such derivatives. In which Y is one selected from formulae (II) to (III). In which Z is selected from formulae (IV) to (VI), and wherein R1, R2, R3, R4, R5, R6, R7 and n are as defined in the claims.

  本发明旨在提供具有强抗疟活性和抗菌活性，且神经系统副作用少的新型抗疟疾化合物，以及一种新的对映选择性途径，允许访问这种化合物的甲氟喹胺类似物。本发明涉及公式(I)的新型4-氨基醇喹啉衍生物，以及这种衍生物的合成方法和用途，其中Y是从公式(II)到(III)中选择的一个，Z是从公式(IV)到(VI)中选择的一个，R1、R2、R3、R4、R5、R6、R7和n如权利要求所定义。
• Structure–activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum
  作者：Erin Milner、William McCalmont、Jayendra Bhonsle、Diana Caridha、Dustin Carroll、Sean Gardner、Lucia Gerena、Montip Gettayacamin、Charlotte Lanteri、ThuLan Luong、Victor Melendez、Jay Moon、Norma Roncal、Jason Sousa、Anchalee Tungtaeng、Peter Wipf、Geoffrey Dow

  DOI：10.1016/j.bmcl.2010.01.001

  日期：2010.2

  Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product pro. le for malaria chemoprophylaxis while reducing permeability across the blood-brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure activity relationship for this library of quinoline methanols. Published by Elsevier Ltd.