4-(二甲基氨基)苯甲酸6-乙酰基-2,3-二甲氧基苯基酯 | 1205548-01-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 中文名称: 4-(二甲基氨基)苯甲酸6-乙酰基-2,3-二甲氧基苯基酯
• 英文名称: 6-acetyl-2,3-dimethoxyphenyl 4-(dimethylamino)benzoate
• 英文别名: 4-(Dimethylamino)benzoic Acid 6-Acetyl-2,3-dimethoxyphenyl Ester；(6-acetyl-2,3-dimethoxyphenyl) 4-(dimethylamino)benzoate
• CAS: 1205548-01-1
• 化学式: C₁₉H₂₁NO₅
• 分子量: 343.379
• InChiKey: GKAMOVUCTDWATB-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(二甲基氨基)苯甲酸6-乙酰基-2,3-二甲氧基苯基酯 在 吡啶 、 硫酸 、 溶剂黄146 、 potassium hydroxide 作用下， 反应 15.0h， 生成 2-(4-(dimethylamino)phenyl)-7,8-dimethoxy-4H-chromen-4-one
  参考文献：
  名称：

  走向原肌球蛋白相关激酶B（TrkB）受体配体的PET脑成像：放射性合成和2-（4- [ 18 F]氟苯基）-7,8-dihydroxy-4 H -chromen-4-one和2-的评估。（4-（[[ N-甲基-11 C]-二甲基氨基）苯基）-7,8-二羟基-4 H-铬-4--4-

  摘要：

  原肌球蛋白相关激酶B（TrkB）与同源配体脑源性神经营养因子（BDNF）的相互作用介导了神经系统发育的基本途径。TrkB信号改变与许多神经退行性疾病和状况有关。在这里，我们报告基于最近确定的7,8-二羟基黄酮化学型的第一个TrkB放射性配体的合成，生物学评估和放射性合成。通过高效的S N Ar放射性氟化，涉及对位-，以高放射化学收率合成了2-（4- [ 18 F]氟苯基）-7,8-二羟基-4 H -chromen-4-one（[ 18 F] 10b）。迈克尔受体取代的芳基，接着是BBr 3-促进的双去甲基化。选择性的N- [ 11 C]甲基化得到2-（4-（[ N-甲基-11 C]-二甲基氨基）苯基）-7,8-二羟基-4 H-铬烯-4-酮（[ 11 C] 10c）从具有[ 11 C] MeOTf的完全脱保护的含邻苯二酚的去甲甲基前体13中分离得到。[ 18 F] 10b的体外放射自显影具有

  DOI：

  10.1016/j.bmc.2013.10.012
• 作为产物：
  描述：

  4-二甲氨基苯甲酰氯 、 2'-羟基-3',4'-二甲氧基苯乙酮 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到4-(二甲基氨基)苯甲酸6-乙酰基-2,3-二甲氧基苯基酯
  参考文献：
  名称：

  走向原肌球蛋白相关激酶B（TrkB）受体配体的PET脑成像：放射性合成和2-（4- [ 18 F]氟苯基）-7,8-dihydroxy-4 H -chromen-4-one和2-的评估。（4-（[[ N-甲基-11 C]-二甲基氨基）苯基）-7,8-二羟基-4 H-铬-4--4-

  摘要：

  原肌球蛋白相关激酶B（TrkB）与同源配体脑源性神经营养因子（BDNF）的相互作用介导了神经系统发育的基本途径。TrkB信号改变与许多神经退行性疾病和状况有关。在这里，我们报告基于最近确定的7,8-二羟基黄酮化学型的第一个TrkB放射性配体的合成，生物学评估和放射性合成。通过高效的S N Ar放射性氟化，涉及对位-，以高放射化学收率合成了2-（4- [ 18 F]氟苯基）-7,8-二羟基-4 H -chromen-4-one（[ 18 F] 10b）。迈克尔受体取代的芳基，接着是BBr 3-促进的双去甲基化。选择性的N- [ 11 C]甲基化得到2-（4-（[ N-甲基-11 C]-二甲基氨基）苯基）-7,8-二羟基-4 H-铬烯-4-酮（[ 11 C] 10c）从具有[ 11 C] MeOTf的完全脱保护的含邻苯二酚的去甲甲基前体13中分离得到。[ 18 F] 10b的体外放射自显影具有

  DOI：

  10.1016/j.bmc.2013.10.012

文献信息

• Treating various disorders with 7,8-dihydroxyflavone and derivatives thereof
  申请人：Ye Keqiang

  公开号：US09895344B2

  公开（公告）日：2018-02-20

  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.

  提供了与激活TrkB受体相关的新化合物和方法。这些方法包括在体内或体外给予治疗有效量的7,8-二羟基黄酮或其衍生物。具体提供了用于治疗包括神经疾病、神经精神疾病和代谢性疾病（如肥胖症）的方法和化合物。例如，提供了第一种方法，用于治疗或减少受试者患抑郁症、焦虑症或肥胖症的风险，包括选择患有或有发展抑郁症、焦虑症或肥胖症风险的受试者，并向受试者给予治疗有效量的7,8-二羟基黄酮或其衍生物。还提供了另一种促进受试者神经保护的方法，包括选择需要神经保护的受试者，并向受试者给予治疗有效量的7,8-二羟基黄酮或其衍生物。
• 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。
• TRKB AGONISTS AND METHODS OF USE
  申请人：Emory University

  公开号：US20150174107A1

  公开（公告）日：2015-06-25

  Compounds and methods related to the activation of the TrkB receptor are provided. The methods include administering a 7,8-dihydroxyflavone 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.

  提供与TrkB受体激活相关的化合物和方法。这些方法包括向需要的受试者施用具有修饰黄酮或杂环环的7,8-二羟基黄酮衍生物。提供用于治疗神经系统疾病、神经精神疾病和代谢性疾病（例如肥胖症）的方法和化合物。
• 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.
• US9504674B2
  申请人：——

  公开号：US9504674B2

  公开（公告）日：2016-11-29