(E )-ethyl 3-(2,3-dimethoxyphenylamino)-3-(4-fluorophenyl)acrylate | 1254973-32-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E )-ethyl 3-(2,3-dimethoxyphenylamino)-3-(4-fluorophenyl)acrylate
• 英文别名: ethyl (E)-3-(2,3-dimethoxyanilino)-3-(4-fluorophenyl)prop-2-enoate
• CAS: 1254973-32-4
• 化学式: C₁₉H₂₀FNO₄
• 分子量: 345.371
• InChiKey: YQINJAVBVCQGKT-FOWTUZBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E )-ethyl 3-(2,3-dimethoxyphenylamino)-3-(4-fluorophenyl)acrylate 以 二苯醚 为溶剂， 反应 0.17h， 生成 2-(4-fluorophenyl)-7,8-dimethoxyquinolin-4(1H)-one
  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
• 作为产物：
  描述：

  4-氟苯甲酰乙酸乙酯 、 2,3-二甲氧基苯胺 在 calcium sulfate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 144.0h， 生成 (E )-ethyl 3-(2,3-dimethoxyphenylamino)-3-(4-fluorophenyl)acrylate
  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

• TRKB AGONISTS AND METHODS OF USE
  申请人：Ye Keqiang

  公开号：US20130040947A1

  公开（公告）日：2013-02-14

  Compounds and methods related to the activation of the TrkB receptor are provided. The methods include administering a 7,8-di-hydroxyflavone derivative with modified flavone or heterocyclic ring to a subject in need thereof. Methods and compounds for the treatment of disorders including neurologic disorders, neuropsychiatric disorders, and metabolic disorders (e.g., obesity) are provided.

  本文提供与TrkB受体激活相关的化合物和方法。这些方法包括将带有改性黄酮或杂环环的7,8-二羟基黄酮衍生物注射给需要的受试者。本文还提供了治疗神经系统疾病、神经精神疾病和代谢性疾病（例如肥胖症）的方法和化合物。
• US9029561B2
  申请人：——

  公开号：US9029561B2

  公开（公告）日：2015-05-12
• US9504674B2
  申请人：——

  公开号：US9504674B2

  公开（公告）日：2016-11-29
• 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.