5-fluoro-4-hydroxy-3-methoxy-3,4-dihydroquinolin-2(1H)-one | 1159706-56-5

• 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: 5-fluoro-4-hydroxy-3-methoxy-3,4-dihydroquinolin-2(1H)-one
• 英文别名: 5-fluoro-4-hydroxy-3-methoxy-3,4-dihydro-1H-quinolin-2-one
• CAS: 1159706-56-5
• 化学式: C₁₀H₁₀FNO₃
• 分子量: 211.193
• InChiKey: ZOURGERPLRWTQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-fluoro-4-hydroxy-3-methoxy-3,4-dihydroquinolin-2(1H)-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以91%的产率得到5-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：

  甲氧基乙酸乙酯 、 2-氟-6-氨基苯甲醛 在 lithium hexamethyldisilazane 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.33h， 以65%的产率得到5-fluoro-4-hydroxy-3-methoxy-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  [EN] HYDROXYQUINOLIN-2(1H)-ONES AND DERIVATIVES THEREOF
  [FR] HYDROXYQUINOLIN-2(1H)-ONES ET LEURS DÉRIVÉS

  摘要：

  这项发明涉及已知和新型的羟基喹啉-2(1H)-酮及其衍生物，可用于治疗哺乳动物（例如人类）的认知相关障碍和神经病性疼痛障碍。该发明还涉及含有这类化合物的药物组合物。

  公开号：

  WO2010058314A1

文献信息

• [EN] HYDROXYQUINOLIN-2(1H)-ONES AND DERIVATIVES THEREOF<br/>[FR] HYDROXYQUINOLIN-2(1H)-ONES ET LEURS DÉRIVÉS
  申请人：PFIZER

  公开号：WO2010058314A1

  公开（公告）日：2010-05-27

  This invention relates to known and novel hydroxyquinolin-2(1H)-ones and derivatives thereof which are useful for the treatment of cognitive-related disorders and neuropathic pain disorders in a mammal, e.g., a human. The invention also relates to pharmaceutical compositions containing such compounds.

  这项发明涉及已知和新型的羟基喹啉-2(1H)-酮及其衍生物，可用于治疗哺乳动物（例如人类）的认知相关障碍和神经病性疼痛障碍。该发明还涉及含有这类化合物的药物组合物。
• Discovery, SAR, and Pharmacokinetics of a Novel 3-Hydroxyquinolin-2(1<i>H</i>)-one Series of Potent <scp>d</scp>-Amino Acid Oxidase (DAAO) Inhibitors
  作者：Allen J. Duplantier、Stacey L. Becker、Michael J. Bohanon、Kris A. Borzilleri、Boris A. Chrunyk、James T. Downs、Lain-Yen Hu、Ayman El-Kattan、Larry C. James、Shenping Liu、Jiemin Lu、Noha Maklad、Mahmoud N. Mansour、Scot Mente、Mary A. Piotrowski、Subas M. Sakya、Susan Sheehan、Stefanus J. Steyn、Christine A. Strick、Victoria A. Williams、Lei Zhang

  DOI：10.1021/jm900128w

  日期：2009.6.11

  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.