ethyl 7-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate | 167758-07-8

• 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 7-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 7-chloro-4-hydroxy-1-methyl-2-oxoquinoline-3-carboxylate
• CAS: 167758-07-8
• 化学式: C₁₃H₁₂ClNO₄
• 分子量: 281.696
• InChiKey: GDHYTXXGCFTUOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 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 7-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate 生成 7-chloro-N'-dodecanoyl-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbohydrazide
  参考文献：
  名称：

  Heterocyclic GSK-3 Allosteric Modulators

  摘要：

  本发明涉及杂环取代喹啉衍生物作为糖原合酶激酶-3（GSK-3）酶的异构抑制剂。因此，这些化合物可用于制造用于治疗和/或预防GSK-3涉及的疾病，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。

  公开号：

  US20160113918A1
• 作为产物：
  描述：

  4-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 10.0h， 生成 ethyl 7-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders:  Structure−Activity Relationship

  摘要：

  Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).

  DOI：

  10.1021/jm031044w

文献信息

• 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。
• Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases
  作者：Valle Palomo、Daniel I. Perez、Carlos Roca、Cara Anderson、Natalia Rodríguez-Muela、Concepción Perez、Jose A. Morales-Garcia、Julio A. Reyes、Nuria E. Campillo、Ana M. Perez-Castillo、Lee L. Rubin、Lubov Timchenko、Carmen Gil、Ana Martinez

  DOI：10.1021/acs.jmedchem.7b00395

  日期：2017.6.22

  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.
• 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