4-amino-3-[1-(2-fluoro-1,1'-biphenyl-4-yl)ethyl]-1,2,4-triazole-5-thione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-3-[1-(2-fluoro-1,1'-biphenyl-4-yl)ethyl]-1,2,4-triazole-5-thione
• 英文别名: 4-amino-5-(1-(2-fluorobiphenyl-4-yl)ethyl)-2H-1,2,4-triazole-3(4H)-thione；4-amino-3-(1-(3-fluoro-4-phenylphenyl)ethyl)-1H-1,2,4-triazole-5(4H)-thione；4-amino-3-[1-(3-fluoro-4-phenylphenyl)ethyl]-1H-1,2,4-triazole-5-thione
• 化学式: C₁₆H₁₅FN₄S
• 分子量: 314.386
• InChiKey: VLQRNQXSFHXROI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-3-[1-(2-fluoro-1,1'-biphenyl-4-yl)ethyl]-1,2,4-triazole-5-thione 、 alkaline earth salt of/the/ methylsulfuric acid 以 乙醇 为溶剂， 以57%的产率得到3-[1-(2-fluoro-1,1'-biphenyl-4-yl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine
  参考文献：
  名称：

  Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins

  摘要：

  Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then similar to 5 mu M (IC50) were further analyzed and showed to induce apoptotic cell death and SubG(1) cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3 beta, beta-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer. (c) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2016.01.013
• 作为产物：
  描述：

  氟比洛芬 在 硫酸 、 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 26.0h， 生成 4-amino-3-[1-(2-fluoro-1,1'-biphenyl-4-yl)ethyl]-1,2,4-triazole-5-thione
  参考文献：
  名称：

  氟比洛芬，布洛芬和4-叔丁基苯甲酰肼的1,2,4-三唑-3-硫酮衍生物的碳酸酐酶抑制潜能：设计，合成，表征，生化评估，分子对接和动态模拟研究

  摘要：

  背景：碳酸酐酶的过度表达会导致某些特定的癌症，包括胰腺癌，胃癌和脑癌。在低氧条件下区分肿瘤，正在进行各种研究以靶向肿瘤的已知低氧区域，以增加对标准治疗的敏感性。 目的：本文中，我们设计并合成了一些生物学上重要的酯，酰肼，硫代氨基甲酸酯，1,2,4-三唑-3-硫酮和席夫碱。该研究的目的是评估该衍生物对碳酸酐酶的作用，并评估相同化合物的毒性。 方法：通过FT-IR，质谱，元素分析，1H和13C NMR光谱对所有化合物的结构进行表征。通过体外测定筛选合成衍生物对碳酸酐酶II的抑制潜力。构建了有效化合物抑制动力学的双倒数图，并确定了抑制方式。此外，为了检查细胞毒性，通过MTT方法测试了这些衍生物对人乳腺腺癌的作用。 结果：化合物10、14和15的X射线衍射分析表明，它们没有任何π-π或CH…π相互作用。通过分子对接和对酶活性口袋中有效化合物的动态模拟，验证了实验结果。揭示了有效化合物与碳酸酐酶酶活

  DOI：

  10.2174/1573406414666181012165156

文献信息

• 布洛芬三唑硫醇衍生物及其在制备新冠病毒抑制剂中应用
  申请人：湖南大学

  公开号：CN113735788A

  公开（公告）日：2021-12-03

  本发明涉及结构式Ⅰ或Ⅱ所示的布洛芬三唑硫醇衍生物或布洛芬三唑硫酮衍生物、其制备方法、药物组合物及其在制备新型冠状病毒3CL蛋白酶抑制剂的应用。布洛芬三唑硫酮是布洛芬三唑硫醇衍生物的互变异构体。其中R选自：氢、氘、C1～C2烷基、C3～C7直链或C3～C7支链烷基；Z选自：氢、4‑氟、4‑羟基、2‑(2,6‑二氯苯氨基)、4‑异丁基、3‑氟‑4‑苯基、3‑苯氧基、3‑苯甲酰基、4‑(2‑甲基烯丙氨基)或4‑(2‑氧代环戊甲基)；Y1、Y2和Y4选自：氢、氘、C1～C2烷基、硝基、氨基、氟、氯、溴、碘、羟基、甲氧基或乙氧基；Y3选自：氢、氘、C1～C2烷基、羟基、乙氧基、硝基、氨基、甲氨基、二甲氨基、乙酰氨基、氟、氯、溴或碘；Y5选自：氢、氘、C1～C2烷基、硝基、氨基、氟、氯、溴或碘。
• Carbonic Anhydrase Inhibitory Potential of 1,2,4-triazole-3-thione Derivatives of Flurbiprofen, Ibuprofen and 4-tert-butylbenzoic Hydrazide: Design, Synthesis, Characterization, Biochemical Evaluation, Molecular Docking and Dynamic Simulation Studies
  作者：Saghir Abbas、Sumera Zaib、Shafiq Ur Rahman、Saqib Ali、Shahid Hameed、Muhammad N. Tahir、Khurram S. Munawar、Farzana Shaheen、Syed M. Abbas、Jamshed Iqbal

  DOI：10.2174/1573406414666181012165156

  日期：2019.4.12

  Background: The over-expression of the carbonic anhydrases results in some specific carcinomas including pancreatic, gastric and brain tumor. Tumors are distinguished under hypoxic conditions and various investigations are being carried out to target the known hypoxic areas of the tumors to increase the sensitivity towards standard therapeutic treatment. Objective: Herein, we have designed and synthesized some

  背景：碳酸酐酶的过度表达会导致某些特定的癌症，包括胰腺癌，胃癌和脑癌。在低氧条件下区分肿瘤，正在进行各种研究以靶向肿瘤的已知低氧区域，以增加对标准治疗的敏感性。 目的：本文中，我们设计并合成了一些生物学上重要的酯，酰肼，硫代氨基甲酸酯，1,2,4-三唑-3-硫酮和席夫碱。该研究的目的是评估该衍生物对碳酸酐酶的作用，并评估相同化合物的毒性。 方法：通过FT-IR，质谱，元素分析，1H和13C NMR光谱对所有化合物的结构进行表征。通过体外测定筛选合成衍生物对碳酸酐酶II的抑制潜力。构建了有效化合物抑制动力学的双倒数图，并确定了抑制方式。此外，为了检查细胞毒性，通过MTT方法测试了这些衍生物对人乳腺腺癌的作用。 结果：化合物10、14和15的X射线衍射分析表明，它们没有任何π-π或CH…π相互作用。通过分子对接和对酶活性口袋中有效化合物的动态模拟，验证了实验结果。揭示了有效化合物与碳酸酐酶酶活
• Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins
  作者：Peri S. Aytaç、Irem Durmaz、Douglas R. Houston、Rengül Çetin-Atalay、Birsen Tozkoparan

  DOI：10.1016/j.bmc.2016.01.013

  日期：2016.2

  Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then similar to 5 mu M (IC50) were further analyzed and showed to induce apoptotic cell death and SubG(1) cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3 beta, beta-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer. (c) 2016 Published by Elsevier Ltd.