ethyl 5-chloro-6-fluoro-3-hydroxy-2-oxo-1,2-dihydroquinoline-4-carboxylate | 1159706-49-6

• 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: ethyl 5-chloro-6-fluoro-3-hydroxy-2-oxo-1,2-dihydroquinoline-4-carboxylate
• 英文别名: ethyl 5-chloro-6-fluoro-3-hydroxy-2-oxo-1H-quinoline-4-carboxylate
• CAS: 1159706-49-6
• 化学式: C₁₂H₉ClFNO₄
• 分子量: 285.659
• InChiKey: BNZRBJCXVVRTKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-chloro-6-fluoro-3-hydroxy-2-oxo-1,2-dihydroquinoline-4-carboxylate 在 lithium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以9%的产率得到5-chloro-6-fluoro-3-hydroxyquinolin-2(1H)-one
  参考文献：
  名称：

  Discovery, SAR, and Pharmacokinetics of a Novel 3-Hydroxyquinolin-2(1H)-one Series of Potent d-Amino Acid Oxidase (DAAO) Inhibitors

  摘要：

  3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a Biacore assay. Cocrystallization of 2 with the human DAAO enzyme defined the binding site and guided the design of new analogues. The SAR, pharmacokinetics, brain exposure, and effects on cerebellum D-serine are described. Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.

  DOI：

  10.1021/jm900128w
• 作为产物：
  描述：

  重氮乙酸乙酯 、 4-氯-5-氟-1H-吲哚-2,3-二酮 在 二乙胺 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以77%的产率得到ethyl 5-chloro-6-fluoro-3-hydroxy-2-oxo-1,2-dihydroquinoline-4-carboxylate
  参考文献：
  名称：

  Discovery, SAR, and Pharmacokinetics of a Novel 3-Hydroxyquinolin-2(1H)-one Series of Potent d-Amino Acid Oxidase (DAAO) Inhibitors

  摘要：

  3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a Biacore assay. Cocrystallization of 2 with the human DAAO enzyme defined the binding site and guided the design of new analogues. The SAR, pharmacokinetics, brain exposure, and effects on cerebellum D-serine are described. Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.

  DOI：

  10.1021/jm900128w