4-bromo-2,7-bis(trifluoromethyl)quinoline | 35853-47-5

• 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: 4-bromo-2,7-bis(trifluoromethyl)quinoline
• 英文别名: 2,7-Bis(trifluormethyl)-4-bromchinolin；Quinoline, 4-bromo-2,7-bis(trifluoromethyl)-
• CAS: 35853-47-5
• 化学式: C₁₁H₄BrF₆N
• 分子量: 344.054
• InChiKey: ICOTWQFECIUUHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 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：

  4-bromo-2,7-bis(trifluoromethyl)quinoline 以 甲醇 、 乙醇 、 水 为溶剂， 反应 68.0h， 生成 4-<2',7'-bis(trifluoromethyl)quinolin-4'-ylamino>-2,6-bis(dipropylaminomethyl)phenol
  参考文献：
  名称：

  Potential Antimalarials. V. 4-(7′-Trifluoromethylquinolin-4′-Ylamino)Phenols, 4-[2′,7′ and 2',8′-Bis(Trifluoromethyl)Quinolin-4′-Ylamino]Phenols and N4-Substituted 2,7-(and 2,8-)Bis(Trifluoromethyl)-Quinolin-4-Amines

  摘要：

  4-(7′-三氟甲基喹啉-4′-氨基)苯酚及其 2′，7′- 和 2′，8′- 双(三氟甲基)类似物的单曼尼希碱和双曼尼希碱、例如 2,6-双(哌啶-1′-基甲基)-4-(7′-三氟甲基-喹啉-4′-基氨基)苯酚。对感染 vinckei vinckei 疟原虫的小鼠腹腔注射单剂量 100 毫克/千克，4-(7′-三氟甲基-喹啉-4′-基氨基)苯酚的曼尼希碱具有显著的抗疟活性；而其 2′,7′-和 2′,8′-双（三氟甲基）类似物则没有显示出明显的活性。还制备了一些具有脂肪族侧链的 N4 取代的 2,7（和 2,8）- 双（三氟甲基）喹啉-4-胺，但没有活性。这里制备的 2,8-双(三氟甲基)喹啉-4-胺没有保留甲氟喹的血吸虫活性。

  DOI：

  10.1071/ch9851827
• 作为产物：
  描述：

  2,7-双三氟甲基-4-羟基喹啉 在 四磷十氧化物 、 四丁基溴化铵 作用下， 以 甲苯 为溶剂， 反应 3.5h， 以86%的产率得到4-bromo-2,7-bis(trifluoromethyl)quinoline
  参考文献：
  名称：

  Identification of 5-(Aryl/Heteroaryl)amino-4-quinolones as Potent Membrane-Disrupting Agents to Combat Antibiotic-Resistant Gram-Positive Bacteria

  摘要：

  Nosocomial infections caused by resistant Gram-positive organisms are on the rise, presumably due to a combination of factors including prolonged hospital exposure, increased use of invasive procedures, and pervasive antibiotic therapy. Although antibiotic stewardship and infection control measures are helpful, newer agents against multidrug-resistant (MDR) Gram-positive bacteria are urgently needed. Here, we describe our efforts that led to the identification of 5-amino-4-quinolone 111 with exceptionally potent Gram-positive activity with minimum inhibitory concentrations (MICs) ≤0.06 μg/mL against numerous clinical isolates. Preliminary mechanism of action and resistance studies demonstrate that the 5-amino-4-quinolones are bacteriostatic, do not select for resistance, and selectively disrupt bacterial membranes. While the precise molecular mechanism has not been elucidated, the lead compound is nontoxic displaying a therapeutic index greater than 500, is devoid of hemolytic activity, and has attractive physicochemical properties (clog P = 3.8, molecular weight (MW) = 441) that warrant further investigation of this promising antibacterial scaffold for the treatment of Gram-positive infections.

  DOI：

  10.1021/acs.jmedchem.2c01151

文献信息

• Trifluoromethyl substituted analogs of quinine and quinidine
  申请人：Hoffmann-La Roche Inc.

  公开号：US03953453A1

  公开（公告）日：1976-04-27

  Trifluoromethyl substituted analogs of quinine and quinidine are prepared by reacting a 4-quinolyllithium compound with a 4,5-erythro-5-ethyl-(or vinyl)-quinuclidine-2 .xi.-carboxaldehyde or the corresponding quinuclidine-2 .xi.-carboxylic acid alkyl ester. The end products are useful as antimalarial agents.

  三氟甲基取代的奎宁和奎宁啶的类似物是通过将4-喹诺啉锂化合物与4,5-内消旋-5-乙基（或乙烯基）喹诺啉-2 .xi.-羧醛或相应的喹诺啉-2 .xi.-羧酸烷基酯反应制备的。最终产品可用作抗疟疾药物。
• BARLIN, G. B.;TAN, WENG-LAI, AUSTRAL. J. CHEM., 1985, 38, N 12, 1827-1835
  作者：BARLIN, G. B.、TAN, WENG-LAI

  DOI：——

  日期：——
• US3953453A
  申请人：——

  公开号：US3953453A

  公开（公告）日：1976-04-27
• Potential Antimalarials. V. 4-(7′-Trifluoromethylquinolin-4′-Ylamino)Phenols, 4-[2′,7′ and 2',8′-Bis(Trifluoromethyl)Quinolin-4′-Ylamino]Phenols and N4-Substituted 2,7-(and 2,8-)Bis(Trifluoromethyl)-Quinolin-4-Amines
  作者：GB Barlin、WL Tan

  DOI：10.1071/ch9851827

  日期：——

  Mono- and di-Mannich bases of 4-(7′-trifluoromethylquinolin-4′- ylamino )phenol and its 2′,7′- and 2′,8′-bis( trifluoromethyl ) analogues, for example 2,6-bis(piperidin-1′-ylmethyl)-4-(7′-trifluoromethyl- quinolin-4′-ylamino)phenol, have been prepared. The Mannich bases from 4-(7′-trifluoromethyl-quinolin-4′-ylamino)phenol showed significant antimalarial activity when injected intraperitoneally in a single dose of 100 mg/kg to mice infected with Plasmodium vinckei vinckei ; those from its 2′,7′- and 2′,8′-bis( trifluoromethyl ) analogues did not show appreciable activity. Some N4-substituted 2,7(and 2,8)- bis ( trifluoromethyl )quinolin-4-amines with aliphatic side chains were also prepared but were inactive. The blood schizontocidal activity of mefloquine was not retained in the 2,8-bis( trifluoromethyl )-quinolin-4-amines prepared here.

  4-(7′-三氟甲基喹啉-4′-氨基)苯酚及其 2′，7′- 和 2′，8′- 双(三氟甲基)类似物的单曼尼希碱和双曼尼希碱、例如 2,6-双(哌啶-1′-基甲基)-4-(7′-三氟甲基-喹啉-4′-基氨基)苯酚。对感染 vinckei vinckei 疟原虫的小鼠腹腔注射单剂量 100 毫克/千克，4-(7′-三氟甲基-喹啉-4′-基氨基)苯酚的曼尼希碱具有显著的抗疟活性；而其 2′,7′-和 2′,8′-双（三氟甲基）类似物则没有显示出明显的活性。还制备了一些具有脂肪族侧链的 N4 取代的 2,7（和 2,8）- 双（三氟甲基）喹啉-4-胺，但没有活性。这里制备的 2,8-双(三氟甲基)喹啉-4-胺没有保留甲氟喹的血吸虫活性。
• Identification of 5-(Aryl/Heteroaryl)amino-4-quinolones as Potent Membrane-Disrupting Agents to Combat Antibiotic-Resistant Gram-Positive Bacteria
  作者：John R. Schultz、Stephen K. Costa、Gorakhnath R. Jachak、Pooja Hegde、Matthew Zimmerman、Yan Pan、Michaele Josten、Chinedu Ejeh、Travis Hammerstad、Hans Georg Sahl、Pedro M. Pereira、Mariana G. Pinho、Véronique Dartois、Ambrose Cheung、Courtney C. Aldrich

  DOI：10.1021/acs.jmedchem.2c01151

  日期：2022.10.27

  Nosocomial infections caused by resistant Gram-positive organisms are on the rise, presumably due to a combination of factors including prolonged hospital exposure, increased use of invasive procedures, and pervasive antibiotic therapy. Although antibiotic stewardship and infection control measures are helpful, newer agents against multidrug-resistant (MDR) Gram-positive bacteria are urgently needed. Here, we describe our efforts that led to the identification of 5-amino-4-quinolone 111 with exceptionally potent Gram-positive activity with minimum inhibitory concentrations (MICs) ≤0.06 μg/mL against numerous clinical isolates. Preliminary mechanism of action and resistance studies demonstrate that the 5-amino-4-quinolones are bacteriostatic, do not select for resistance, and selectively disrupt bacterial membranes. While the precise molecular mechanism has not been elucidated, the lead compound is nontoxic displaying a therapeutic index greater than 500, is devoid of hemolytic activity, and has attractive physicochemical properties (clog P = 3.8, molecular weight (MW) = 441) that warrant further investigation of this promising antibacterial scaffold for the treatment of Gram-positive infections.