4-chloro-2-(4-fluorophenyl)-6-nitroquinoline | 1416440-17-9

• 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-chloro-2-(4-fluorophenyl)-6-nitroquinoline
• 英文别名: 4-Chloro-2-(4-fluorophenyl)-6-nitroquinoline
• CAS: 1416440-17-9
• 化学式: C₁₅H₈ClFN₂O₂
• 分子量: 302.692
• InChiKey: RUVVXIVEHPNTMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-2-(4-fluorophenyl)-6-nitroquinoline 在 盐酸 、 sodium azide 、 乙醇 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 乙酸乙酯 为溶剂， 反应 30.0h， 生成 N6-[2-amino-6-(2-pyridyl)pyrimidin-4-yl]-2-(4-fluorophenyl)quinoline-4,6-diamine
  参考文献：
  名称：

  Quinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB Agents

  摘要：

  NDH-2 is an essential respiratory enzyme in Mycobacterium tuberculosis (Mtb), which plays an important role in the physiology of Mtb. Herein, we present a target-based effort to identify a new structural class of inhibitors for NDH-2. High-throughput screening of the AstraZeneca corporate collection resulted in the identification of quinolinyl pyrimidines as the most promising class of NDH-2 inhibitors. Structure-activity relationship studies showed improved enzyme inhibition (IC50) against the NDH-2 target, which in turn translated into cellular activity against Mtb. Thus, the compounds in this class show a good correlation between enzyme inhibition and cellular potency. Furthermore, early ADME profiling of the best compounds showed promising results and highlighted the quinolinyl pyrimidine class as a potential lead for further development.

  DOI：

  10.1021/ml300134b
• 作为产物：
  描述：

  4-氟苯甲酰乙酸乙酯 在 盐酸 、 Dowtherm A 、 三氯氧磷 作用下， 以 正丁醇 为溶剂， 反应 54.0h， 生成 4-chloro-2-(4-fluorophenyl)-6-nitroquinoline
  参考文献：
  名称：

  Quinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB Agents

  摘要：

  NDH-2 is an essential respiratory enzyme in Mycobacterium tuberculosis (Mtb), which plays an important role in the physiology of Mtb. Herein, we present a target-based effort to identify a new structural class of inhibitors for NDH-2. High-throughput screening of the AstraZeneca corporate collection resulted in the identification of quinolinyl pyrimidines as the most promising class of NDH-2 inhibitors. Structure-activity relationship studies showed improved enzyme inhibition (IC50) against the NDH-2 target, which in turn translated into cellular activity against Mtb. Thus, the compounds in this class show a good correlation between enzyme inhibition and cellular potency. Furthermore, early ADME profiling of the best compounds showed promising results and highlighted the quinolinyl pyrimidine class as a potential lead for further development.

  DOI：

  10.1021/ml300134b

文献信息

• Synthesis and <i>In Vitro</i> Biological Evaluation of Quinolinyl Pyrimidines Targeting Type II NADH-Dehydrogenase (NDH-2)
  作者：Lu Lu、Linda Åkerbladh、Shabbir Ahmad、Vivek Konda、Sha Cao、Anthony Vocat、Louis Maes、Stewart T. Cole、Diarmaid Hughes、Mats Larhed、Peter Brandt、Anders Karlén、Sherry L. Mowbray

  DOI：10.1021/acsinfecdis.1c00413

  日期：2022.3.11

  Type II NADH dehydrogenase (NDH-2) is an essential component of electron transfer in many microbial pathogens but has remained largely unexplored as a potential drug target. Previously, quinolinyl pyrimidines were shown to inhibit Mycobacterium tuberculosis NDH-2, as well as the growth of the bacteria [Shirude, P. S.; ACS Med. Chem. Lett. 2012, 3, 736−740]. Here, we synthesized a number of novel quinolinyl

  II 型 NADH 脱氢酶 (NDH-2) 是许多微生物病原体中电子转移的重要组成部分，但作为潜在的药物靶点仍未被广泛探索。以前，喹啉基嘧啶被证明可以抑制结核分枝杆菌NDH-2，以及细菌的生长 [施鲁德，PS; ACS医学。化学。莱特。 2012 年，第 3期，第 736-740 页]。在这里，我们合成了许多新型喹啉基嘧啶并研究了它们的性质。在抑制来自结核分枝杆菌和耻垢分枝杆菌的 NDH-2 酶方面，最好的化合物与先前报道的同类抑制剂具有相似的效力（半最大抑制浓度（IC 50）在低微米范围内的值）。然而，许多化合物对革兰氏阴性病原体具有更好的活性，最低抑菌浓度 (MIC) 低至 2 μg/mL。多变量分析（偏最小二乘法 (PLS) 和主成分分析 (PCA)）表明，总体配体电荷是决定抗菌活性的最重要因素之一，其模式因特定细菌种类而异。在某些情况下（例如，分枝杆菌），IC 50之间存在明显的相关性值和观察到的