3-[1-(6-methoxynaphtalen-2-yl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[1-(6-methoxynaphtalen-2-yl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine
• 英文别名: 3-(1-(6-methoxynaphthalen-2-yl)ethyl)-6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine；3-[1-(6-methoxynaphthalen-2-yl)ethyl]-6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• 化学式: C₂₃H₂₀N₄OS
• 分子量: 400.504
• InChiKey: CLOICWPWSSMQCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  77.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 以 乙醇 为溶剂， 反应 1.0h， 生成 3-[1-(6-methoxynaphtalen-2-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

文献信息

• Structural alterations based on naproxen scaffold: Synthesis, evaluation of antitumor activity and COX-2 inhibition, and molecular docking
  作者：Walaa M. El-Husseiny、Magda A.-A. El-Sayed、Naglaa I. Abdel-Aziz、Adel S. El-Azab、Yousif A. Asiri、Alaa A.-M. Abdel-Aziz

  DOI：10.1016/j.ejmech.2018.09.007

  日期：2018.10

  testing showed that the compounds 4b, 6c, 10b, and 10c exhibited effective COX-2 inhibition, with IC50 values of 0.40–1.20 μM, and selectivity index (SI) values of >62.50–20.83, using celecoxib as a reference drug (IC50 = 0.11 μM; COX-2 SI: >227.20). Compounds 6c and 10c, which were potent COX-2 inhibitors, were docked into the COX-2 binding site, where these compounds exhibited strong interactions.

  一系列新的非羧酸萘普生类似物中，轴承的各种环体系，如恶二唑的3A-C和6A-C ，环烷烃图4a-d ，环状酰亚胺5A-C ，和三唑7 - 9和图10A-C ，是合成的。此外，在体外抗肿瘤活性和环加氧酶的同功酶（COX-1 / COX-2）靶的抑制试验化合物3 - 10进行了研究。抗肿瘤活性测定的结果表明化合物4b，6c，10b和10c对被测细胞系MCF-7，MDA-231，HeLa和HCT-116表现出最大的抗肿瘤活性，IC 50范围为4.83–14.49μM。相比之下，参考药物阿霉素，阿法替尼和塞来昔布的IC 50值分别为3.18–26.79、6.20–11.40和22.79–42.74μM。此外，体外COX-1 / COX-2抑制试验表明，化合物4b，6c，10b和10c表现出有效的COX-2抑制作用，IC 50值为0.40–1.20μM，选择性指数（SI）值为> 62.50–20.83，使用塞来昔布作为参考药物（IC