4-N-quinolin-3-yl-6-[4-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine | 1393883-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-N-quinolin-3-yl-6-[4-(trifluoromethyl)phenyl]pyrimidine-2,4-diamine
• CAS: 1393883-12-9
• 化学式: C₂₀H₁₄F₃N₅
• 分子量: 381.36
• InChiKey: SMMLKIDIYFHBBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-amino-6-(4-(trifluoromethyl)phenyl)pyrimidin-4-ol 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 为溶剂， 反应 12.0h， 生成 4-N-quinolin-3-yl-6-[4-(trifluoromethyl)phenyl]pyrimidine-2,4-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

文献信息

• Quinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB Agents
  作者：Pravin S. Shirude、Beena Paul、Nilanjana Roy Choudhury、Chaitanya Kedari、Balachandra Bandodkar、Bheemarao G. Ugarkar

  DOI：10.1021/ml300134b

  日期：2012.9.13

  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.