4-allyl-5-(2-phenylquinolin-4-yl)-4H-1,2,4-triazole-3-thiol | 847503-25-7

• 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-allyl-5-(2-phenylquinolin-4-yl)-4H-1,2,4-triazole-3-thiol
• 英文别名: 3-(2-phenylquinolin-4-yl)-4-prop-2-enyl-1H-1,2,4-triazole-5-thione
• CAS: 847503-25-7
• 化学式: C₂₀H₁₆N₄S
• mdl: MFCD03423482
• 分子量: 344.44
• InChiKey: GAAMMPVKKCDGCD-UHFFFAOYSA-N

物化性质

• 沸点：
  514.2±60.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-（4-乙酰基苯基）-2-溴乙酰胺 、 4-allyl-5-(2-phenylquinolin-4-yl)-4H-1,2,4-triazole-3-thiol 在 三乙胺 作用下， 以 乙腈 为溶剂， 以60%的产率得到N-(4-acetylphenyl)-2-((4-allyl-5-(2-phenylquinolin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetamide
  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：

  2-苯基-4-喹啉羧酸 在 硫酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 15.0h， 生成 4-allyl-5-(2-phenylquinolin-4-yl)-4H-1,2,4-triazole-3-thiol
  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/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