2-(4-fluorophenyl)-7,8-dihydroxyquinolin-4(1H)-one hydrobromide | 1205548-05-5

• 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: 2-(4-fluorophenyl)-7,8-dihydroxyquinolin-4(1H)-one hydrobromide
• 英文别名: 2-(4-fluorophenyl)-7,8-dihydroxy-1H-quinolin-4-one;hydrobromide
• CAS: 1205548-05-5
• 化学式: BrH*C₁₅H₁₀FNO₃
• 分子量: 352.16
• InChiKey: GRJMTLKEMZQRBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 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：
  69.6
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(4-fluorophenyl)-7,8-dimethoxyquinolin-4(1H)-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以44%的产率得到2-(4-fluorophenyl)-7,8-dihydroxyquinolin-4(1H)-one hydrobromide
  参考文献：
  名称：

  A Synthetic 7,8-Dihydroxyflavone Derivative Promotes Neurogenesis and Exhibits Potent Antidepressant Effect

  摘要：

  7,8-Dihydroxyflavone is a recently identified small molecular tropomyosin-receptor-kinase B (TrkB) agonist. Our preliminary structural activity relationship (SAR) study showed that the 7,8-dihydroxy groups are essential for the agonistic effect. To improve the lead compound's agonistic activity, we have conducted an extensive SAR study and synthesized numerous derivatives. We have successfully identified 4'-dimethylamino-7,8-dihydroxyflavone that displays higher TrkB agonistic activity than that of the lead. This novel compound also exhibits a more robust and longer TrkB activation effect in animals. Consequently, this new compound reveals more potent antiapoptotic activity. Interestingly, chronic oral administration of 4'-dimethylamino-7,8-dihydroxyflavone and its lead strongly promotes neurogenesis in dentate gyrus and demonstrates marked antidepressant effects. Hence, our data support that the synthetic 4'-dimethylamino-7,8-dihydroxyflavone and its lead both are orally bioavailable TrkB agonists and possess potent antidepressant effects.

  DOI：

  10.1021/jm101206p

文献信息

• TREATING VARIOUS DISORDERS WITH 7,8-DIHYDROXYFLAVONE AND DERIVATIVES THEREOF
  申请人：Ye Keqiang

  公开号：US20110144196A1

  公开（公告）日：2011-06-16

  Novel compounds and methods related to the activation of the TrkB receptor are provided. The methods include administering in vivo or in vitro a therapeutically effective amount of 7,8-dihydroxyflavone or derivative thereof. Specifically, methods and compounds for the treatment of disorders including neurologic disorders, neuropsychiatric disorders, and metabolic disorders (e.g., obesity) are provided. For example, a first method is provided of treating or reducing the risk of depression, anxiety, or obesity in a subject, which includes selecting a subject with or at risk of developing depression, anxiety, or obesity, and administering to the subject a therapeutically effective amount of 7,8-dihydroxyflavone or a derivative thereof. A further method of promoting neuroprotection in a subject also is provided, which includes selecting a subject in need of neuroprotection, and administering to the subject a therapeutically effective amount of 7,8-dihydroxyflavone or a derivative thereof.

  本发明提供了与TrkB受体激活相关的新化合物和方法。该方法包括在体内或体外给予7,8-二羟基黄酮或其衍生物的治疗有效量。具体提供了用于治疗神经疾病、神经精神疾病和代谢性疾病（例如肥胖症）的方法和化合物。例如，提供了一种用于治疗或减少患者患抑郁症、焦虑症或肥胖症风险的第一种方法，其中包括选择患有或有发展抑郁症、焦虑症或肥胖症风险的患者，并向该患者给予7,8-二羟基黄酮或其衍生物的治疗有效量。还提供了一种促进患者神经保护的进一步方法，包括选择需要神经保护的患者，并向该患者给予7,8-二羟基黄酮或其衍生物的治疗有效量。
• US9895344B2
  申请人：——

  公开号：US9895344B2

  公开（公告）日：2018-02-20
• A Synthetic 7,8-Dihydroxyflavone Derivative Promotes Neurogenesis and Exhibits Potent Antidepressant Effect
  作者：Xia Liu、Chi-Bun Chan、Sung-Wuk Jang、Sompol Pradoldej、Junjian Huang、Kunyan He、Lien H. Phun、Stefan France、Ge Xiao、Yonghui Jia、Hongbo R. Luo、Keqiang Ye

  DOI：10.1021/jm101206p

  日期：2010.12.9

  7,8-Dihydroxyflavone is a recently identified small molecular tropomyosin-receptor-kinase B (TrkB) agonist. Our preliminary structural activity relationship (SAR) study showed that the 7,8-dihydroxy groups are essential for the agonistic effect. To improve the lead compound's agonistic activity, we have conducted an extensive SAR study and synthesized numerous derivatives. We have successfully identified 4'-dimethylamino-7,8-dihydroxyflavone that displays higher TrkB agonistic activity than that of the lead. This novel compound also exhibits a more robust and longer TrkB activation effect in animals. Consequently, this new compound reveals more potent antiapoptotic activity. Interestingly, chronic oral administration of 4'-dimethylamino-7,8-dihydroxyflavone and its lead strongly promotes neurogenesis in dentate gyrus and demonstrates marked antidepressant effects. Hence, our data support that the synthetic 4'-dimethylamino-7,8-dihydroxyflavone and its lead both are orally bioavailable TrkB agonists and possess potent antidepressant effects.