1-异丁基-4-羟基-2-氧代-1,2-二氢喹啉-3-羧酸乙酯 | 303776-43-4

• 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
• 中文名称: 1-异丁基-4-羟基-2-氧代-1,2-二氢喹啉-3-羧酸乙酯
• 英文名称: ethyl 4-hydroxy-1-isobutyl-2-oxo-1,2-dihydroquinoline-3-carboxylate
• 英文别名: 3-Quinolinecarboxylic acid, 1,2-dihydro-4-hydroxy-1-(2-methylpropyl)-2-oxo-, ethyl ester；ethyl 4-hydroxy-1-(2-methylpropyl)-2-oxoquinoline-3-carboxylate
• CAS: 303776-43-4
• 化学式: C₁₆H₁₉NO₄
• 分子量: 289.331
• InChiKey: FBWUQHGLLKKQIH-UHFFFAOYSA-N

物化性质

• 沸点：
  408.1±45.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  1-异丁基-4-羟基-2-氧代-1,2-二氢喹啉-3-羧酸乙酯 在 sodium t-butanolate 作用下， 以 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 反应 12.0h， 生成 N-(4-fluoro-3-(4-methylpiperazin-1-yl)phenyl)-4-hydroxy-1-isobutyl-2-oxo-1,2-dihydroquinoline-3-carboxamide monoformate salt
  参考文献：
  名称：

  [EN] NOTCH INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE NOTCH ET LEURS UTILISATIONS

  摘要：

  本公开的内容包括用于抑制Notch的化合物及其用途。

  公开号：

  WO2021237112A1
• 作为产物：
  描述：

  2-(isobutylamino)benzoic acid 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 、 乙酸乙酯 、 mineral oil 为溶剂， 反应 5.25h， 生成 1-异丁基-4-羟基-2-氧代-1,2-二氢喹啉-3-羧酸乙酯
  参考文献：
  名称：

  [EN] NOTCH INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE NOTCH ET LEURS UTILISATIONS

  摘要：

  本公开的内容包括用于抑制Notch的化合物及其用途。

  公开号：

  WO2021237112A1

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。
• 4-hydroxy-2-quinolones. 191.* synthesis, tautomerism and biological activity of benzimidazol-2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids
  作者：I. V. Ukrainets、L. A. Grinevich、A. A. Tkach、O. V. Gorokhova、V. N. Kravchenko、G. Sim

  DOI：10.1007/s10593-011-0673-8

  日期：2011.2

  A series of benzimidazol-2-ylamides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids was prepared in a search for biologically active compounds. These compounds exist in the crystal exclusively in the amide form, while in solution amide↔imide tautomerism is observed. The results of a study of the antithyroid and antituberculosis activities of these compounds are given.

  为了寻找生物活性化合物，制备了一系列4-羟基-2-氧代-1,2-二氢喹啉-3-羧酸的苯并咪唑-2-基酰胺。这些化合物仅以酰胺形式存在于晶体中，而在溶液中则观察到酰胺↔酰亚胺互变异构现象。给出了这些化合物的抗甲状腺和抗结核活性的研究结果。
• 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。
• WO2007/38571
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.