2-(4-chlorophenyl)-6-methoxyquinoline-4-carboxylic acid

• 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: 2-(4-chlorophenyl)-6-methoxyquinoline-4-carboxylic acid
• 英文别名: 2-[p-Chlorophenyl]-6-methoxycinchoninic acid
• 化学式: C₁₇H₁₂ClNO₃
• 分子量: 313.74
• InChiKey: ZYGKAANTHMYWGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)-6-methoxyquinoline-4-carboxylic acid 在 硫酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 17.0h， 生成 5-(2-(4-chlorophenyl)-6-methoxyquinolin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol
  参考文献：
  名称：

  NO-releasing STAT3 inhibitors suppress BRAF-mutant melanoma growth

  摘要：

  Constitutive activation of STAT3 can play a vital role in the development of melanoma. STAT3-targeted therapeutics are reported to show efficacy in melanomas harboring the BRAFV600E mutant and also in vemurafenib-resistant melanomas. We designed and synthesized a series of substituted nitric oxide (NO)-releasing quinolone-1,2,4-triazoleioxime hybrids, hypothesizing that the introduction of a STAT3 binding scaffold would augment their cytotoxicity. All the hybrids tested showed a comparable level of in vitro NO production. 7b and 7c exhibited direct binding to the STAT3-SH domain with IC50 of similar to 0.5 mu M. Also, they abrogated STAT3 tyrosine phosphorylation in several cancer cell lines, including the A375 melanoma cell line that carries the BRAFV600E mutation. At the same time, they did not affect the phosphorylation of upstream kinases or other STAT isoforms. 7c inhibited STAT3 nuclear translocation in mouse embryonic fibroblast while 7b and 7c inhibited STAT3 DNA-binding activity in the A375 cell line. Their anti-proliferating activity is attributed to their ability to trigger the production of reactive oxygen species and induce G1 cell cycle arrest in the A375 cell line. Interestingly, 7b and 7c showed robust cell growth suppression and apoptosis induction in two pairs of BRAF inhibitor-naive (-S) and resistant (-R) melanoma cell lines containing a BRAF V600E mutation. Surprisingly, MEL1617-R cells that are known to be more resistance to MEK inhibition by GSK1120212 than MEL1617-S cells exhibit a similar response to 7b and 7c. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111885
• 作为产物：
  描述：

  5-甲氧基靛红 、 对氯苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 以71%的产率得到2-(4-chlorophenyl)-6-methoxyquinoline-4-carboxylic acid
  参考文献：
  名称：

  新型喹啉/查尔酮杂化物作为抗癌剂：细胞毒性和PI3K抑制活性的设计，合成和评估。

  摘要：

  设计了一系列喹啉-查耳酮杂化物作为潜在的抗癌药，进行了合成和评估。不同的细胞毒性试验表明，化合物具有良好的活性。化合物9i和9j对所有测试的A549和K-562细胞的IC50 = 1.91-5.29 µM的细胞系最有效。从机理上讲，9i和9j诱导了A549和K562细胞的G2 / M细胞周期停滞和凋亡。此外，当针对两种提及的化合物进行测试时，所有PI3K亚型均被非选择性抑制，IC50为52-473 nM，其中9i对PI3K-γ最有效（IC50 = 52 nM）。9i和9j的对接显示可能在PI3K-γ同工型的活性位点与基本缬氨酸残基形成H键。同时，Western印迹分析显示9i和9j抑制了PI3K，Akt，mTOR，以及A549和K562细胞中的GSK-3β，提示阻断PI3K / Akt / mTOR途径与上述抗肿瘤活性相关。总之，我们的发现通过抑制PI3K / Akt / mTOR途径，支

  DOI：

  10.1016/j.bioorg.2018.10.064

文献信息

• New quinoline/chalcone hybrids as anti-cancer agents: Design, synthesis, and evaluations of cytotoxicity and PI3K inhibitory activity
  作者：Samar H. Abbas、Amer Ali Abd El-Hafeez、Mai E. Shoman、Monica M. Montano、Heba A. Hassan

  DOI：10.1016/j.bioorg.2018.10.064

  日期：2019.2

  A series of quinoline-chalcone hybrids was designed as potential anti-cancer agents, synthesized and evaluated. Different cytotoxic assays revealed that compounds experienced promising activity. Compounds 9i and 9j were the most potent against all the cell lines tested with IC50 = 1.91-5.29 µM against A549 and K-562 cells. Mechanistically, 9i and 9j induced G2/M cell cycle arrest and apoptosis in both

  设计了一系列喹啉-查耳酮杂化物作为潜在的抗癌药，进行了合成和评估。不同的细胞毒性试验表明，化合物具有良好的活性。化合物9i和9j对所有测试的A549和K-562细胞的IC50 = 1.91-5.29 µM的细胞系最有效。从机理上讲，9i和9j诱导了A549和K562细胞的G2 / M细胞周期停滞和凋亡。此外，当针对两种提及的化合物进行测试时，所有PI3K亚型均被非选择性抑制，IC50为52-473 nM，其中9i对PI3K-γ最有效（IC50 = 52 nM）。9i和9j的对接显示可能在PI3K-γ同工型的活性位点与基本缬氨酸残基形成H键。同时，Western印迹分析显示9i和9j抑制了PI3K，Akt，mTOR，以及A549和K562细胞中的GSK-3β，提示阻断PI3K / Akt / mTOR途径与上述抗肿瘤活性相关。总之，我们的发现通过抑制PI3K / Akt / mTOR途径，支
• Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II
  作者：Said A.H. El-Feky、Zakaria K. Abd El-Samii、Nermine A. Osman、Jasmine Lashine、Mohamed A. Kamel、Hamdy Kh. Thabet

  DOI：10.1016/j.bioorg.2014.12.003

  日期：2015.2

  In continuation of our study of novel quinolines with anti-inflammatory activity using the Pfitzinger reaction, several new quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds

  在我们继续使用Pfitzinger反应研究具有抗炎活性的新型喹啉中，合成了几种新的喹啉衍生物，并测试了它们的抗炎和促溃疡作用。对目标化合物进行了COX-2结合口袋的对接研究，以合理化它们对COX-2酶的可能选择性。发现活性最高的化合物（5a，8a和11a）优于塞来昔布。化合物11a表现出最高的抗炎活性以及与COX-2结合位点的最佳结合特性。此外，化合物9c，9e，10a和11a没有致溃疡活性。
• A green synthesis of quinoline‐4‐carboxylic derivatives using <i>p</i> ‐toluenesulfonic acid as an efficient organocatalyst under microwave irradiation and their docking, molecular dynamics, ADME‐Tox and biological evaluation
  作者：Dhaval B. Patel、Dhanji P. Rajani、Smita D. Rajani、Hitesh D. Patel

  DOI：10.1002/jhet.3848

  日期：2020.4

  used for the preparation of quinoline‐4‐carboxylic acid derivatives via a one‐pot three‐component reaction of aromatic benzaldehyde, substituted aniline, and pyruvic acid under microwave irradiation. After completion of the reaction, the pure products were isolated by column chromatography. Here, to achieve the desired synthesis, various catalytic and solvent conditions were applied to perform a comparison

  P‐甲苯磺酸是一种高效，无害且可快速获得的有机催化剂，用于在微波辐射下通过芳族苯甲醛，取代的苯胺和丙酮酸的一锅三组分反应制备喹啉-4-羧酸衍生物。 。反应完成后，通过柱色谱法分离纯产物。在这里，为了实现所需的合成，应用了各种催化和溶剂条件进行比较研究。我们正在使用更高的收率，简单的后处理工艺，避免使用有害的有机溶剂，缩短反应时间以及在研究中使用本协议的更高优势。测试了合成化合物针对各种抗菌，抗真菌，抗疟和抗结核菌株的生物活性。化合物发现4a和4c（MIC 50μg/ mL）和化合物4d和4n（MIC 62.5μg/ mL）对大肠杆菌菌株具有活性，化合物4c和4p（MIC 25μg/ mL）对金黄色葡萄球菌菌株具有活性，发现化合物4c和4d对恶性疟原虫菌株具有活性。分子对接表明配体和蛋白质恰好适合结合口袋，并与生物活性显着相关。我们还测试了合成化合物的分子动力学和ADME-Tox参数。
• Antimalarials. 7-Chloro-4-hydroxy- and 4,7-Dichloro-1-methylcarbostyrils¹
  作者：Robert E. Lutz、John F. Codington、Russell J. Rowlett、Adolf J. Deinet、Philip S. Bailey

  DOI：10.1021/ja01213a041

  日期：1946.9
• NO-releasing STAT3 inhibitors suppress BRAF-mutant melanoma growth
  作者：Tamer S. Kaoud、Aliaa M. Mohassab、Heba A. Hassan、Chunli Yan、Sabrina X. Van Ravenstein、Dalia Abdelhamid、Kevin N. Dalby、Mohamed Abdel-Aziz

  DOI：10.1016/j.ejmech.2019.111885

  日期：2020.1

  Constitutive activation of STAT3 can play a vital role in the development of melanoma. STAT3-targeted therapeutics are reported to show efficacy in melanomas harboring the BRAFV600E mutant and also in vemurafenib-resistant melanomas. We designed and synthesized a series of substituted nitric oxide (NO)-releasing quinolone-1,2,4-triazoleioxime hybrids, hypothesizing that the introduction of a STAT3 binding scaffold would augment their cytotoxicity. All the hybrids tested showed a comparable level of in vitro NO production. 7b and 7c exhibited direct binding to the STAT3-SH domain with IC50 of similar to 0.5 mu M. Also, they abrogated STAT3 tyrosine phosphorylation in several cancer cell lines, including the A375 melanoma cell line that carries the BRAFV600E mutation. At the same time, they did not affect the phosphorylation of upstream kinases or other STAT isoforms. 7c inhibited STAT3 nuclear translocation in mouse embryonic fibroblast while 7b and 7c inhibited STAT3 DNA-binding activity in the A375 cell line. Their anti-proliferating activity is attributed to their ability to trigger the production of reactive oxygen species and induce G1 cell cycle arrest in the A375 cell line. Interestingly, 7b and 7c showed robust cell growth suppression and apoptosis induction in two pairs of BRAF inhibitor-naive (-S) and resistant (-R) melanoma cell lines containing a BRAF V600E mutation. Surprisingly, MEL1617-R cells that are known to be more resistance to MEK inhibition by GSK1120212 than MEL1617-S cells exhibit a similar response to 7b and 7c. (C) 2019 Elsevier Masson SAS. All rights reserved.