ethyl 6-chloro-1-ethyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate | 697255-92-8

• 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 6-chloro-1-ethyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate
• 英文别名: (3Z)-6-chloro-3-[ethoxy(hydroxy)methylidene]-1-ethylquinoline-2,4-dione；ethyl 6-chloro-1-ethyl-4-hydroxy-2-oxoquinoline-3-carboxylate
• CAS: 697255-92-8
• 化学式: C₁₄H₁₄ClNO₄
• 分子量: 295.722
• InChiKey: KSHXYSCRQMFKFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  月桂酰肼 、 ethyl 6-chloro-1-ethyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.05h， 以74%的产率得到6-chloro-N'-dodecanoyl-1-ethyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide
  参考文献：
  名称：

  Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases

  摘要：

  Glycogen synthase kinase 3 beta (GSK-3 beta) is a central target in several unmet diseases. To increase the specificity of GSK-3 beta inhibitors in chronic treatments, we developed small molecules allowing subtle modulation of GSK-3 beta activity. Design synthesis, structure activity relationships, and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3 beta are presented here. Furthermore, we show how allosteric binders may overcome the beta-catenin side effects associated with strong GSK-3 beta inhibition. The therapeutic potential of some of these modulators has been tested in human samples from patients with congenital myotonic dystrophy type 1 (CDM1) and spinal it atrophy (SMA) patients. We found that compound 53 improves delayed myogenesis in CDM1 myoblasts, while compounds 1 and 53 have neuroprotective properties in SMA-derived cells. These findings suggest that the allosteric modulators of GSK-3 beta may be used for future development of drugs for DM1, SMA, and other chronic diseases where GSK-3 beta inhibition exhibits therapeutic effects.

  DOI：

  10.1021/acs.jmedchem.7b00395
• 作为产物：
  描述：

  5-氯靛红酸酐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 ethyl 6-chloro-1-ethyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases

  摘要：

  Glycogen synthase kinase 3 beta (GSK-3 beta) is a central target in several unmet diseases. To increase the specificity of GSK-3 beta inhibitors in chronic treatments, we developed small molecules allowing subtle modulation of GSK-3 beta activity. Design synthesis, structure activity relationships, and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3 beta are presented here. Furthermore, we show how allosteric binders may overcome the beta-catenin side effects associated with strong GSK-3 beta inhibition. The therapeutic potential of some of these modulators has been tested in human samples from patients with congenital myotonic dystrophy type 1 (CDM1) and spinal it atrophy (SMA) patients. We found that compound 53 improves delayed myogenesis in CDM1 myoblasts, while compounds 1 and 53 have neuroprotective properties in SMA-derived cells. These findings suggest that the allosteric modulators of GSK-3 beta may be used for future development of drugs for DM1, SMA, and other chronic diseases where GSK-3 beta inhibition exhibits therapeutic effects.

  DOI：

  10.1021/acs.jmedchem.7b00395

文献信息

• Heterocyclic GSK-3 Allosteric Modulators
  申请人：Consejo Superior de Investigaciones Cientificas (CSIC)

  公开号：US20150057311A1

  公开（公告）日：2015-02-26

  The present invention relates to heterocyclic substituted quinoline derivatives as allosteric inhibitors of the glycogen synthase kinase-3 (GSK-3) enzyme. Therefore, these compounds are useful for the manufacturing of a medicament designed for the treatment and/or prevention of diseases wherein GSK-3 is involved, such as neurodegenerative diseases, inflammatory diseases, cancer, diabetes, and to promote various regenerative processes.

  本发明涉及杂环取代喹啉衍生物作为糖原合成酶激酶-3 (GSK-3) 酶的变构抑制剂。因此，这些化合物可用于制造用于治疗和/或预防 GSK-3 参与的疾病的药物，例如神经退行性疾病、炎症性疾病、癌症、糖尿病，以及促进各种再生过程。
• Heterocyclic GSK-3 allosteric modulators
  申请人：Consejo Superior de Investigaciones Cientificas (CSIC)

  公开号：US09193688B2

  公开（公告）日：2015-11-24

  The present invention relates to heterocyclic substituted quinoline derivatives as allosteric inhibitors of the glycogen synthase kinase-3 (GSK-3) enzyme. Therefore, these compounds are useful for the manufacturing of a medicament designed for the treatment and/or prevention of diseases wherein GSK-3 is involved, such as neurodegenerative diseases, inflammatory diseases, cancer, diabetes, and to promote various regenerative processes.

  本发明涉及杂环取代的喹啉衍生物作为糖原合成酶激酶-3（GSK-3）酶的变构抑制剂。因此，这些化合物可用于制造用于治疗和/或预防GSK-3参与的疾病，如神经退行性疾病、炎症性疾病、癌症、糖尿病以及促进各种再生过程的药物。
• HETEROCYCLIC GSK-3 ALLOSTERIC MODULATORS
  申请人：Consejo Superior De Investigaciones Científicas (CSIC)

  公开号：EP2769720B1

  公开（公告）日：2017-03-29
• US9193688B2
  申请人：——

  公开号：US9193688B2

  公开（公告）日：2015-11-24
• US9585879B2
  申请人：——

  公开号：US9585879B2

  公开（公告）日：2017-03-07