4-(2-methylquinolin-4-yl)morpholine | 82607-87-2

• 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: 4-(2-methylquinolin-4-yl)morpholine
• 英文别名: 2-methyl-4-morpholinoquinoline；2-methyl-4-morpholino-quinoline；2-Methyl-4-morpholino-chinolin；2-methyl-4-morpholin-4-yl-quinoline
• CAS: 82607-87-2
• 化学式: C₁₄H₁₆N₂O
• mdl: MFCD06009945
• 分子量: 228.294
• InChiKey: MVHYZDDSGBXCEZ-UHFFFAOYSA-N

物化性质

• 熔点：
  95 °C(Solv: carbon tetrachloride (56-23-5); ligroine (8032-32-4))
• 沸点：
  409.0±45.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-methylquinolin-4-yl)morpholine 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 以70%的产率得到4-morpholinoquinoline-2-carbaldehyde
  参考文献：
  名称：

  合成和评估新的喹啉衍生物抑制hnRNP K调节癌基因c-myc转录。

  摘要：

  异质核糖核蛋白K（hnRNP K）的异常过表达是许多人类癌症的发生和发展的关键特征。已发现hnRNP K是上调c-myc基因转录的转录激活因子，c-myc基因转录是调节细胞生长和分化的关键原癌基因。因此，通过破坏hnRNP K破坏其与c-myc基因启动子的结合来抑制c-myc转录是癌症治疗的一种潜在方法。在本研究中，我们合成并筛选了一系列喹啉衍生物，并评估了它们对hnRNP K的结合亲和力。在这些衍生物中，（E）-1-（4-甲氧基苯基）-3-（4-吗啉代-6-硝基喹啉-确定2-（基）丙-2-烯-1-酮（化合物25）是第一个报告的hnRNP K结合配体，其KD值为4.6和2。用SPR和MST分别测得6μM。随后的评估表明，化合物25与hnRNP K的结合可破坏其c-myc启动子i-motif的展开，从而导致c-myc转录的下调。化合物25对人癌细胞系表现出选择性的抗增殖作用，IC50值为1.36至3

  DOI：

  10.1016/j.bioorg.2018.12.020
• 作为产物：
  描述：

  4-羟基-2-甲基喹啉 在 对甲苯磺酸 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-(2-methylquinolin-4-yl)morpholine
  参考文献：
  名称：

  合成和评估新的喹啉衍生物抑制hnRNP K调节癌基因c-myc转录。

  摘要：

  异质核糖核蛋白K（hnRNP K）的异常过表达是许多人类癌症的发生和发展的关键特征。已发现hnRNP K是上调c-myc基因转录的转录激活因子，c-myc基因转录是调节细胞生长和分化的关键原癌基因。因此，通过破坏hnRNP K破坏其与c-myc基因启动子的结合来抑制c-myc转录是癌症治疗的一种潜在方法。在本研究中，我们合成并筛选了一系列喹啉衍生物，并评估了它们对hnRNP K的结合亲和力。在这些衍生物中，（E）-1-（4-甲氧基苯基）-3-（4-吗啉代-6-硝基喹啉-确定2-（基）丙-2-烯-1-酮（化合物25）是第一个报告的hnRNP K结合配体，其KD值为4.6和2。用SPR和MST分别测得6μM。随后的评估表明，化合物25与hnRNP K的结合可破坏其c-myc启动子i-motif的展开，从而导致c-myc转录的下调。化合物25对人癌细胞系表现出选择性的抗增殖作用，IC50值为1.36至3

  DOI：

  10.1016/j.bioorg.2018.12.020

文献信息

• Recyclable Catalysts for Palladium-Catalyzed Aminations of Aryl Halides
  作者：Andreas Dumrath、Christa Lübbe、Helfried Neumann、Ralf Jackstell、Matthias Beller

  DOI：10.1002/chem.201100984

  日期：2011.8.22

  Aminated and recycled: Palladium/imidazolium phosphane catalysts enable efficient and general aminations of aryl halides, including direct amination with ammonia. Subsequent recycling is possible without any additional heterogenization (see scheme).

  胺化和再循环：钯/咪唑鎓膦催化剂可实现芳基卤化物的有效和常规胺化，包括直接氨化。随后的回收是可能的，而无需进行任何其他异化处理（请参阅方案）。
• 2-Propene-1-Ones As Hsp 70 Inducers
  申请人：Kumar Prabhat

  公开号：US20080207608A1

  公开（公告）日：2008-08-28

  The present invention relates to novel compounds of 2-propene-1-one series, of general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them, wherein R 5 , R 6 , Q and Y are as defined in the specification. The present invention also relates to a process for preparing such compounds, compositions containing such compounds, and use of such compound and composition in medicine. The compounds of the general formula (I) induce HSP-70 and are useful for the treatment of diseases accompanying pathological stress in a living mammalian organism, including a human being, such as stroke, myocardial infarction, inflammatory disorder, hepatotoxicity, sepsis, diseases of viral origin, allograft rejection, tumourous diseases, gastric mucosal damage, brain haemorrhage, endothelial dysfunctions, diabetic complications, neuro-degenerative diseases, post-traumatic neuronal damage, acute renal failure, glaucoma and aging related skin degeneration.

  本发明涉及2-丙烯酮系列的新化合物，通式为（I），它们的衍生物，类似物，互变异构体，立体异构体，多晶形，药学上可接受的盐，药学上可接受的溶剂和含有它们的药学上可接受的组合物，其中R5，R6，Q和Y如规范中所定义。本发明还涉及制备这种化合物的过程，含有这种化合物的组合物，以及在医学上使用这种化合物和组合物。通式（I）的化合物诱导HSP-70，并用于治疗伴随病理应激的疾病，包括中风，心肌梗死，炎症性疾病，肝毒性，败血症，病毒性疾病，异体移植排斥，肿瘤性疾病，胃黏膜损伤，脑出血，内皮功能障碍，糖尿病并发症，神经退行性疾病，创伤后神经损伤，急性肾衰竭，青光眼和与衰老相关的皮肤退化。
• [EN] 2-PROPENE-1-ONES AS HSP 70 INDUCERS<br/>[FR] 2-PROPENE-1-ONES UTILISES COMME INDUCTEURS DE HSP 70
  申请人：TORRENT PHARMACEUTICALS LTD

  公开号：WO2005097746A3

  公开（公告）日：2006-01-19
• Developing Inhibitors of the p47phox–p22phox Protein–Protein Interaction by Fragment-Based Drug Discovery
  作者：Sara Marie Øie Solbak、Jie Zang、Dilip Narayanan、Lars Jakobsen Høj、Saskia Bucciarelli、Charlotte Softley、Sebastian Meier、Annette Eva Langkilde、Charlotte Held Gotfredsen、Michael Sattler、Anders Bach

  DOI：10.1021/acs.jmedchem.9b01492

  日期：2020.2.13

  Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phox(SH3A-B)) with K-D values of 400-600 mu M. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phox(SH3A-B) and these competed with p22phox for binding to p47phox(SH3A-B). Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phox(SH3A-B)-p22phox interaction (K-i of 20 mu M). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.
• Further studies on the cyclization of aromatic azomethines ortho-substituted with a trifluoromethyl group: synthesis of 2,4-di- or 2,3,4-trisubstituted quinolines
  作者：Lucjan Strekowski、Steven E. Patterson、Lubomir Janda、Roman L. Wydra、Donald B. Harden、Malgorzata Lipowska、Marek T. Cegla

  DOI：10.1021/jo00027a037

  日期：1992.1

  The scope and limitations of the novel synthetic route to quinolines (Strekowski et al. J. Org. Chem. 1990, 55, 4777) have been studied. A direct condensation of 2-(trifluoromethyl)aniline (1) with methyl aryl ketones, methyl heteroaryl ketones, ethyl aryl ketones, methyl vinyl ketones, 1-indanone, 1-tetralone, camphor, and cyclohexanone provides an easy access to the corresponding ketimines. An indirect one-pot preparation of dialkyl ketimines and C-alkyl-substituted amidines derived from 1, but inaccessible by the direct condensation method, is also presented. All these ketimines and amidines are cyclized in the presence of alkylamide, dialkylamide, or alkoxide bases to give a quinoline containing the base function at C-4. Analysis of byproducts of the base-mediated reactions provides strong support for the originally proposed mechanism of the quinoline formation.