4-chloro-6-methoxyquinolin-2(1H)-one | 1029773-70-3

• 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: 4-chloro-6-methoxyquinolin-2(1H)-one
• 英文别名: 4-Chloro-6-methoxyquinolin-2(1H)-one；4-chloro-6-methoxy-1H-quinolin-2-one
• CAS: 1029773-70-3
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.632
• InChiKey: NRPRRUSWUPMVRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-6-methoxyquinolin-2(1H)-one 在 一水合肼 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 diethyl 2-(2-(6-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)hydrazono)succinate
  参考文献：
  名称：

  Novel Pyrazoloquinolin-2-ones: Design, synthesis, docking studies, and biological evaluation as antiproliferative EGFR-TK inhibitors

  摘要：

  Two new series of diethyl 2-[2-(substituted-2-oxo-1,2-dihydroquinolin-4-yl)hydrazono]-succinates 6a-g and 1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazoles 7a-f have been designed and synthesized. The structures of the synthesized compounds were proved by IR, mass, NMR (2D) spectra and elemental analyses. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI protocol. Consequently, seven compounds were further examined against the most sensitive cell lines, leukemia CCRFCEM, and MOLT-4. 5-Amino-1-(6-bromo-2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazole-3,4-dicarbonitrile (7f) was the most active product, with IC50= 1.35 uM and 2.42 uM against MOLT-4 and CCRF-CEM, respectively. Also, it showed a remarkable inhibitory activity compared to erlotinib on the EGFR TK with IC50 = 247.14 nM and 208.42 nM, respectively. Cell cycle analysis of MOLT-4 cells treated with 7f showed cell cycle arrest at G2/M phase (supported by Caspases, BAX and Bcl-2 studies) with a significant pro-apoptotic activity as indicated by annexin V-FITC staining. Moreover, the docking study indicated that both the pyrazole moiety and the quinolin-2-one ring showed good fitting into EGFR (PDB code: 1M17). In order to interpret SAR of the designed compounds, and provide a basis for further optimization, molecular docking of the synthesized compounds to known EGFR inhibitors was performed. The study illustrated the effect of several factors on the compounds' activity.

  DOI：

  10.1016/j.bioorg.2019.103045
• 作为产物：
  描述：

  在 溶剂黄146 作用下， 生成 4-chloro-6-methoxyquinolin-2(1H)-one
  参考文献：
  名称：

  新的喹啉-2-酮/吡唑衍生物；设计，合成，分子对接，抗凋亡评估和caspase-3抑制分析。

  摘要：

  我们报告了新的喹啉-2-一/吡唑杂化物的合成及其抗凋亡活性。使用N-乙酰半胱氨酸（NAC）作为抗凋亡参考，研究了减少I / R诱导的大鼠结肠组织损伤的效果。与模型组相比，化合物6a，6c和6f的氧化应激参数MDA，SOD，GSH和NOx表现出显着改善，并且比参考NAC（N-乙酰半胱氨酸）更大，而化合物6d和6e与模型组相比显示出较弱的抗氧化活性。参考NAC。此外，与模型组相比，化合物6a，6c和6f显示出炎性介质TNFα和CRB的降低显着大于NAC，尤其是化合物6c，其与conc 2.13mg / dL的NAC相比发现CRB为1.90（mg / dL）。此外，对所有目标化合物进行了结肠组织病理学研究，结果表明，与NAC相比，化合物6a和6f的H＆E切片显示明显的正常结肠细胞，而化合物6e显示的血管扩张，凋亡细胞更多。Caspase-3抑制分析表明，化合物6a，6b和6d减弱caspase-3的表达的程度高于NAC（分别为1

  DOI：

  10.1016/j.bioorg.2019.103348

文献信息

• Novel one pot synthesis of 2-amino-4-chloroquinolines via Smiles rearrangement
  作者：Devadoss Karthik Kumar、Subramaniam Parameswaran Rajendran

  DOI：10.1016/j.tetlet.2012.04.028

  日期：2012.6

  We have developed a novel one pot synthesis of 4-chloroquinolin-2-ylamines via Smiles rearrangement under milder condition. The key transformation involves O-alkylation of 4-chloro-1H-quinolin-2-ones with chloroacetamide followed by Smiles rearrangement. The scope of this methodology is further extended to the synthesis of 4-chloroquinolin-2-ylmethylamines and 2-(4-chloroquinolin-2-ylamino)ethanols

  我们已经开发了一种在温和条件下通过Smiles重排合成4-氯喹啉-2-基胺的新型一锅法。关键转化涉及用氯乙酰胺对4-氯-1 H-喹啉-2-酮进行O-烷基化，然后进行Smiles重排。该方法的范围进一步扩展至4-氯喹啉-2-基甲胺和2-（4-氯喹啉-2-基氨基）乙醇的合成。该方法提供了2-氨基-4-氯喹啉的良好产率。
• Identification and molecular modeling of new quinolin-2-one thiosemicarbazide scaffold with antimicrobial urease inhibitory activity
  作者：Mohammed A. I. Elbastawesy、Yaseen A. M. M. El-Shaier、Mohamed Ramadan、Alan B. Brown、Ashraf A. Aly、Gamal El-Din A. Abuo-Rahma

  DOI：10.1007/s11030-019-10021-0

  日期：2021.2

  A new series of 6-substituted quinolin-2-one thiosemicarbazides 6a–j has been synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analyses. All the designed final compounds were evaluated for their in vitro activity against the urease-producing R. mucilaginosa and Proteus mirabilis bacteria as fungal and bacterial pathogens, respectively. Moreover, all compounds were in vitro tested as potential urease inhibitors using the cup-plate diffusion method. Compounds 6a and 6b were the most active with (IC50 = 0.58 ± 0.15 and 0.43 ± 0.09 µM), respectively, in comparison with lead compound I (IC50 = 1.13 ± 0.00 µM). Also, the designed compounds were docked into urease proteins (ID: 3LA4 and ID: 4UBP) using Open Eye® software to understand correctly about ligand–receptor interactions. The docking results revealed that the designed compounds can interact with the active site of the enzyme through multiple strong hydrogen bonds. Moreover, rapid overlay of chemical structures’ analysis was described to understand the 3D QSAR of synthesized compounds as urease inhibitors. The results emphasize the importance of polar thiosemicarbazide directly linked to 6-substituted quinolone moieties as promising antimicrobial urease inhibitors.

  一系列6-取代的喹啉-2-酮硫脲6a–j已被合成。目标化合物的结构通过不同的光谱和元素分析得到证实。所有设计的最终化合物分别对产生脲酶的R. mucilaginosa和Proteus mirabilis细菌作为真菌和细菌病原体的体外活性进行了评估。此外，所有化合物在体外采用杯盘扩散法作为潜在的脲酶抑制剂进行了测试。化合物6a和6b活性最强，分别为（IC50 = 0.58 ± 0.15和0.43 ± 0.09μM），与先导化合物I（IC50 = 1.13 ± 0.00μM）相比。此外，设计的化合物通过Open Eye®软件对接入脲酶蛋白（ID：3LA4和ID：4UBP），以正确理解配体-受体相互作用。对接结果显示，设计的化合物可以通过多个强氢键与酶的活性位点相互作用。此外，还描述了化学结构的快速叠加分析，以理解合成的化合物作为脲酶抑制剂的3D QSAR。结果强调了直接连接到6-取代喹诺酮部分的极性硫脲作为有前途的抗菌脲酶抑制剂的重要性。
• New Quinoline-2-one/thiazolium bromide Derivatives; Synthesis, Characterization and Mechanism of Formation
  作者：Sara M. Mostafa、Ashraf A. Aly、Samia M. Sayed、Mohamed A. Raslan、Amira E. Ahmed、Ayman Nafady、Esam A. Ishak、Ahmed M. Shawky、El-Shimaa M.N. Abdelhafez

  DOI：10.1016/j.molstruc.2021.130501

  日期：2021.9

  We report on the formation of new quinoline-2-one derived by thiazolium bromides from the reaction of 3-thiosemicarbazides derived by 2-quinolones with 2-bromoacetophenones. The structure of products was elucidated by mass, IR and NMR spectra together with elemental analysis. The mechanism of products formation was discussed.

  我们报道了由噻唑溴化物衍生的新喹啉-2-酮的形成，该喹啉-2-酮是由2-喹诺酮与2-溴苯乙酮衍生的3-硫代氨基脲的反应。通过质量，IR和NMR光谱以及元素分析来阐明产物的结构。讨论了产品形成的机理。
• An efficient click synthesis of chalcones derivatized with two 1-(2-quinolon-4-yl)-1,2,3-triazoles
  作者：Mohammed B. Alshammari、Ashraf A. Aly、Alan B. Brown、Md Afroz Bakht、Ahmed M. Shawky、Adel M. Abdelhakem、Essmat M. El-Sheref

  DOI：10.1515/znb-2021-0028

  日期：2021.7.27

  Chalcones derivatized with 1-(2-quinolonyl)-1,2,3-triazoles were synthesized by reaction of 4-azido-2-quinolones with 1-phenyl-3-(4-propargyloxyphenyl)prop-2-en-1-one, or by aldol reaction of 4-[1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes with acetophenone. Whereas, chalcones bearing two 1-(2-quinolonyl)-1,2,3-triazoles were synthesized by reaction of 1,3-bis(4-propargyloxyphenyl)prop-2-en-1-one with 4-azido-2-quinolones, or by aldol condensation between 4-4-[(4-acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl}quinolin-2(1H)-ones and 4-[1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes.

  摘要：通过4-偶氮基-2-喹啉酮与1-苯基-3-(4-丙炔氧基苯基)丙-2-烯-1-酮反应合成了与1-(2-喹啉基)-1,2,3-三唑衍生的香豆素，或者通过4-[1-(2-氧代-1,2-二氢喹啉-4-基)-1H-1,2,3-三唑-4-基]甲氧基}苯甲醛与苯乙酮的醛缩反应合成了。而带有两个1-(2-喹啉基)-1,2,3-三唑的香豆素是通过1,3-双(4-丙炔氧基苯基)丙-2-烯-1-酮与4-偶氮基-2-喹啉酮的反应合成，或者通过4-4-[(4-乙酰基苯氧基)甲基]-1H-1,2,3-三唑-1-基}喹啉-2(1H)-酮与4-[1-(2-氧代-1,2-二氢喹啉-4-基)-1H-1,2,3-三唑-4-基]甲氧基}苯甲醛之间的醛缩反应合成的。
• Syntheses and Fluorescent Properties of 6-Methoxy-2-oxoquinoline-3,4-dicarbonitriles and 6,7-Dimethoxy-2-oxoquinoline-3,4-dicarbonitriles
  作者：Guy Crépin Enoua、Günther Lahm、Georg Uray、Wolfgang Stadlbauer

  DOI：10.1002/jhet.1865

  日期：2014.8

  4-Chlorocarbostyrils , , , , with methoxy substituents in 6, 7, or 6,7-position react with potassium cyanide in a p-toluenesulfinate mediated reaction either to the highly fluorescent and stable 2-oxoquinoline-3,4-dicarbonitriles , , , or at slightly lower temperatures to 4-monocarbonitriles , , . 4-Chlorocarbostyril and lithium p-toluenesulfinate gave pure 4-toluenesulfonylquinolone , which reacted

  4-氯咔啉 ， ， ， ， 在6、7或6,7位的甲氧基取代基与 对甲苯磺酸酯介导的对高荧光和稳定的2-氧代喹啉-3,4-二腈的反应中的氰化钾， ， ， 或在较低的温度下生成4-单腈 ， ， 。4-氯卡巴斯蒂利 和 对甲苯磺酸锂得到纯的4-甲苯磺酰基喹诺酮与氰化钾反应生成单腈 或二腈 ，取决于反应条件。4-三氟甲基喹诺酮类 和 由合适的甲氧基苯胺和4,4,4-三氟乙酰乙酸制备用于荧光比较的样品。