N6-[2-amino-6-(4-chlorophenyl)pyrimidin-4-yl]-2-(3-methoxyphenyl)quinoline-4,6-diamine | 423183-10-2

• 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: N6-[2-amino-6-(4-chlorophenyl)pyrimidin-4-yl]-2-(3-methoxyphenyl)quinoline-4,6-diamine
• 英文别名: 6-N-[2-amino-6-(4-chlorophenyl)pyrimidin-4-yl]-2-(3-methoxyphenyl)quinoline-4,6-diamine
• CAS: 423183-10-2
• 化学式: C₂₆H₂₁ClN₆O
• 分子量: 468.945
• InChiKey: CJSVGJIGUYTIJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (4-氯苯甲酰基)乙酸乙酯 在 盐酸 、 sodium hydride 、 三乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 N6-[2-amino-6-(4-chlorophenyl)pyrimidin-4-yl]-2-(3-methoxyphenyl)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

文献信息

• N-TYPE CALCIUM CHANNEL ANTAGONISTS FOR THE TREATMENT OF PAIN
  申请人：AstraZeneca AB

  公开号：EP1339706B1

  公开（公告）日：2006-04-19
• 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.