6-bromo-1-ethyl-4-hydroxy-N'-octanoyl-2-oxo-1,2-dihydroquinoline-3-carbohydrazide | 1429014-16-3

• 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: 6-bromo-1-ethyl-4-hydroxy-N'-octanoyl-2-oxo-1,2-dihydroquinoline-3-carbohydrazide
• 英文别名: 6-Bromo-1-ethyl-4-hydroxy-N'-octanoyl-2-oxo-1,2-dihydroquinoline-3-carbohydrazide；6-bromo-1-ethyl-4-hydroxy-N'-octanoyl-2-oxoquinoline-3-carbohydrazide
• CAS: 1429014-16-3
• 化学式: C₂₀H₂₆BrN₃O₄
• 分子量: 452.348
• InChiKey: SYUGFUGELINXSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  98.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴靛红酸酐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.05h， 生成 6-bromo-1-ethyl-4-hydroxy-N'-octanoyl-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

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。
• Upgrading polyester wastes with silanes and their blends
  申请人：Armacell Enterprise GmbH & Co. KG

  公开号：EP2770015A1

  公开（公告）日：2014-08-27

  The invention describes a process of polyester waste upgrading by means of a chemical treatment with silanes and their blends as well as the upgraded final product, which is characterized by a semicrystalline structure and improved thermal and hydrolytic stability, resulting from a reduced overall carboxyl content. The polyester waste is mixed with silicon-based modifier(s), wherein the silicon-based modifier(s) are organofunctional silanes and their blends with silicone derivatives, in a total concentration of 0.01-10 wt.%, preferably 0.1-5 wt.%, based on the weight of the polyester waste, wherein the organofunctional silanes are selected from the group of vinyl or divinyl terminated silanes, allyl terminated silanes, amine derivatives of silanes such as 3-aminopropyl- or bis(2-hydroxyethyl)-3-aminopropyl- terminated silanes, 2-(3,4-epoxycyclohexyl)ethyl-, 3-glycidoxypropyl- or similar epoxy derivatives, isocyanotopropyl- or similar isocyanate derivatives, 3-methacryloxypropyl- or similar methacrylate derivatives, 2-(diphenylphosphino)ethyl- or similar phosphine derivatives.

  本发明描述了一种通过硅烷及其混合物进行化学处理的聚酯废料升级工艺，以及升级后的最终产品，该产品的特点是具有半结晶结构，由于总体羧基含量降低，热稳定性和水解稳定性得到改善。聚酯废料与硅基改性剂混合，其中硅基改性剂为有机官能硅烷及其与有机硅衍生物的混合物，总浓度为 0.01-10wt.%，优选 0.1-5wt.%，以聚酯废料重量为基准。其中有机官能团硅烷选自乙烯基或二乙烯基端基硅烷、烯丙基端基硅烷、硅烷的胺衍生物，如 3-氨基丙基或双(2-羟乙基)-3-氨基丙基端基硅烷、2-(3,4-环氧环己基)乙基、3-缩水甘油氧基丙基或类似的环氧衍生物、异氰基丙基或类似的异氰酸酯衍生物、3-甲基丙烯酰氧基丙基或类似的甲基丙烯酸酯衍生物、2-(二苯基膦)乙基或类似的膦衍生物。
• 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