4-chloro-2,7-bis(trifluoromethyl)quinazoline | 959238-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-chloro-2,7-bis(trifluoromethyl)quinazoline
• CAS: 959238-04-1
• 化学式: C₁₀H₃ClF₆N₂
• mdl: MFCD09954899
• 分子量: 300.591
• InChiKey: QZMMXNPFCLSURE-UHFFFAOYSA-N

物化性质

• 沸点：
  192.6±40.0 °C(Predicted)
• 密度：
  1.590±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-chloro-2,7-bis(trifluoromethyl)quinazoline 、 2-氨基-5-三氟甲基吡啶 在 异丙醇 作用下， 反应 17.0h， 以70%的产率得到4-[5-(trifluoromethyl)pyrid-2-yl]-2,7-bis(trifluoromethyl)quinazoline
  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
• 作为产物：
  描述：

  2-氨基-4-三氟甲基苯腈 在 吡啶 、 4-二甲氨基吡啶 、 氯化亚砜 、 双氧水 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 生成 4-chloro-2,7-bis(trifluoromethyl)quinazoline
  参考文献：
  名称：

  [EN] MEMBRANE-ACTIVE ANTI-BACTERIAL COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS ANTIBACTÉRIENS À MEMBRANE ACTIVE ET LEURS UTILISATIONS

  摘要：

  在一种实施例中，本公开涉及抑制细菌生长的方法。一般来说，这些方法包括将细菌暴露于本公开披露的抗细菌化合物中。在某些实施例中，这种暴露发生在体内的受试者中，以治疗或预防细菌感染。在其他实施例中，本公开涉及适用于抑制细菌生长的抗细菌化合物。

  公开号：

  WO2021042046A1

文献信息

• [EN] MEMBRANE-ACTIVE ANTI-BACTERIAL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ANTIBACTÉRIENS À MEMBRANE ACTIVE ET LEURS UTILISATIONS
  申请人：DARTMOUTH COLLEGE

  公开号：WO2021042046A1

  公开（公告）日：2021-03-04

  In an embodiment, the present disclosure pertains to methods of inhibiting bacterial growth. Generally, the methods include exposing bacteria to an anti-bacterial compound as disclosed herein. In some embodiments, the exposing occurs in vivo in a subject in order to treat or prevent a bacterial infection. In additional embodiments, the present disclosure pertains to anti- bacterial compounds that are suitable for inhibiting bacterial growth.

  在一种实施例中，本公开涉及抑制细菌生长的方法。一般来说，这些方法包括将细菌暴露于本公开披露的抗细菌化合物中。在某些实施例中，这种暴露发生在体内的受试者中，以治疗或预防细菌感染。在其他实施例中，本公开涉及适用于抑制细菌生长的抗细菌化合物。
• 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.