2-(4-chlorophenyl)quinoline-4-carbohydrazide

• 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)quinoline-4-carbohydrazide
• 化学式: C₁₆H₁₂ClN₃O
• mdl: MFCD01471407
• 分子量: 297.744
• InChiKey: OPYVMDQJLITFPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)quinoline-4-carbohydrazide 在 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 5.0h， 生成 2-(5-(2-(4-chlorophenyl)quinolin-4-yl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)-N-(4-((E)-3-(4-chlorophenyl)acryloyl)phenyl)acetamide
  参考文献：
  名称：

  新型喹啉/查尔酮/1,2,4-三唑杂化物作为靶向EGFR和BRAFV600E激酶的强效抗增殖剂的设计和合成

  摘要：

  已经设计、合成了含有 1,2,4-三唑部分的新型喹啉/查耳酮杂化物，并通过各种光谱技术阐明和确认了它们的结构。设计的化合物在单剂量试验中对不同的 NCI 60 细胞系显示出中等至良好的活性，生长抑制率为 50% 至 94%。化合物7b、7d、9b和9d是大多数癌细胞系中活性最强的化合物，其生长抑制百分比在 77% 和 94% 之间。评估了新合成的杂交体对一组四种人类癌细胞系的抗增殖活性。化合物7a、7b、9a、9b和9d显示出有希望的抗增殖活性。以厄洛替尼作为参考药物，进一步测试了这些化合物对 EGFR 和 BRAF V600E激酶的抑制效力。化合物7a、7b、9a、9b和9d的分子对接研究表明，它们非常适合 EGFR 和 BRAF V600E激酶的活性位点。化合物7b、9b和9d显示出最高的结合亲和力和与厄洛替尼相似的结合模式。

  DOI：

  10.1016/j.bioorg.2020.104510
• 作为产物：
  描述：

  2-(4-氯苯基)喹啉-4-甲酸 在 硫酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 2-(4-chlorophenyl)quinoline-4-carbohydrazide
  参考文献：
  名称：

  新型喹啉/查尔酮/1,2,4-三唑杂化物作为靶向EGFR和BRAFV600E激酶的强效抗增殖剂的设计和合成

  摘要：

  已经设计、合成了含有 1,2,4-三唑部分的新型喹啉/查耳酮杂化物，并通过各种光谱技术阐明和确认了它们的结构。设计的化合物在单剂量试验中对不同的 NCI 60 细胞系显示出中等至良好的活性，生长抑制率为 50% 至 94%。化合物7b、7d、9b和9d是大多数癌细胞系中活性最强的化合物，其生长抑制百分比在 77% 和 94% 之间。评估了新合成的杂交体对一组四种人类癌细胞系的抗增殖活性。化合物7a、7b、9a、9b和9d显示出有希望的抗增殖活性。以厄洛替尼作为参考药物，进一步测试了这些化合物对 EGFR 和 BRAF V600E激酶的抑制效力。化合物7a、7b、9a、9b和9d的分子对接研究表明，它们非常适合 EGFR 和 BRAF V600E激酶的活性位点。化合物7b、9b和9d显示出最高的结合亲和力和与厄洛替尼相似的结合模式。

  DOI：

  10.1016/j.bioorg.2020.104510

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
• 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.
• New quinoline/1,2,4-triazole hybrids as dual inhibitors of COX-2/5-LOX and inflammatory cytokines: Design, synthesis, and docking study
  作者：Aliaa M. Mohassab、Heba A. Hassan、Dalia Abdelhamid、Ahmed M. Gouda、Hesham A.M. Gomaa、Bahaa G.M. Youssif、Mohamed O. Radwan、Mikako Fujita、Masami Otsuka、Mohamed Abdel-Aziz

  DOI：10.1016/j.molstruc.2021.130948

  日期：2021.11
• Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: Synthesis and preliminary evaluation as antimicrobial agents
  作者：Kamel A. Metwally、Lobna M. Abdel-Aziz、El-Sayed M. Lashine、Mohamed I. Husseiny、Rania H. Badawy

  DOI：10.1016/j.bmc.2006.08.022

  日期：2006.12

  A new series of 2-arylquinoline-4-carboxylic acid hydrazide-hydrazones was synthesized using an appropriate synthetic route. All the target compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus as an example for Gram-positive bacteria, Escherichia coli as an example for Gram-negative bacteria, and Candida albicans as a representative of fungi. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. Among the compounds tested, compounds having nitro substituents at the arylidene moiety showed the most potent antifungal as well as antibacterial activities against E coli. Compound 23 displayed an antifungal activity comparable to that of nystatin. However, none of the compounds demonstrated any antibacterial activity against S. aureus. Hydrophobicity of the target compounds correlated weakly with their antibacterial and antifungal activities. The most potent compounds namely, 7, 18, 19, 22, and 23 were assessed for hemolytic toxicity and found to be non-hemolytic up to a concentration of 100 mu g/mL. In addition, the most potent compound (23) was evaluated for in vitro cytotoxic activity against various cancer cell lines. This compound was found to display no cytotoxic activity but rather it induces the proliferation rate of Hep-G2 cells. (c) 2006 Elsevier Ltd. All rights reserved.
• Design and synthesis of novel quinoline/chalcone/1,2,4-triazole hybrids as potent antiproliferative agent targeting EGFR and BRAFV600E kinases
  作者：Aliaa M. Mohassab、Heba A. Hassan、Dalia Abdelhamid、Ahmed M. Gouda、Bahaa G.M. Youssif、Hiroshi Tateishi、Mikako Fujita、Masami Otsuka、Mohamed Abdel-Aziz

  DOI：10.1016/j.bioorg.2020.104510

  日期：2021.1

  New quinoline / chalcone hybrids containing 1,2,4-triazole moiety have been designed, synthesized and their structures elucidated and confirmed by various spectroscopic techniques. The designed compounds showed moderate to good activity on different NCI 60 cell lines in a single-dose assay with a growth inhibition rate ranging from 50% to 94%. Compounds 7b, 7d, 9b, and 9d were the most active compounds

  已经设计、合成了含有 1,2,4-三唑部分的新型喹啉/查耳酮杂化物，并通过各种光谱技术阐明和确认了它们的结构。设计的化合物在单剂量试验中对不同的 NCI 60 细胞系显示出中等至良好的活性，生长抑制率为 50% 至 94%。化合物7b、7d、9b和9d是大多数癌细胞系中活性最强的化合物，其生长抑制百分比在 77% 和 94% 之间。评估了新合成的杂交体对一组四种人类癌细胞系的抗增殖活性。化合物7a、7b、9a、9b和9d显示出有希望的抗增殖活性。以厄洛替尼作为参考药物，进一步测试了这些化合物对 EGFR 和 BRAF V600E激酶的抑制效力。化合物7a、7b、9a、9b和9d的分子对接研究表明，它们非常适合 EGFR 和 BRAF V600E激酶的活性位点。化合物7b、9b和9d显示出最高的结合亲和力和与厄洛替尼相似的结合模式。