4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-4H-1,2,4-triazole-3-thiol | 225508-94-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-4H-1,2,4-triazole-3-thiol
• 英文别名: 4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-3-mercapto-(4H)-1,2,4-triazole；4-amino-5-(1-(6-methoxynaphthalen-2-yl)ethyl)-4H-1,2,4-triazole-3-thiol；4-amino-3-[1-(6-methoxynaphthalen-2-yl)ethyl]-1H-1,2,4-triazole-5-thione
• CAS: 225508-94-1
• 化学式: C₁₅H₁₆N₄OS
• 分子量: 300.384
• InChiKey: PEENUFMKGXFWCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  95
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-二氯苯甲酸 、 4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-4H-1,2,4-triazole-3-thiol 在 三氯氧磷 作用下， 反应 5.0h， 以59%的产率得到6-(2,4-Dichlorophenyl)-3-[1-(6-methoxynaphthalen-2-yl)ethyl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
  参考文献：
  名称：

  萘普生稠合杂环6-取代-1,2,4-三唑[3,4-b] -1,3,4-噻二唑衍生物的合成及药理评价。

  摘要：

  通过4-氨基-5- [环己基]的环化反应，已经合成了一些6-取代的1,2,4-三唑并[3,4-b] -1,3,4-噻二唑衍生物（4a-f和5a-d）。通过一步反应，将1-（6-甲氧基-2-萘基乙基）-3-巯基-（4H）-1,2,4-三唑（3）与各种取代的芳族酸和芳基/烷基异硫氰酸酯一起使用。通过已知的实验模型，用药理学方法评估目标化合物的抗炎和止痛潜力。其中一些显示出明显的活性。对于有效化合物，观察到极低的致溃疡指数。

  DOI：

  10.1016/j.bmcl.2007.06.003
• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 在 氢氧化钾 、 硫酸 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-4H-1,2,4-triazole-3-thiol
  参考文献：
  名称：

  萘普生稠合杂环6-取代-1,2,4-三唑[3,4-b] -1,3,4-噻二唑衍生物的合成及药理评价。

  摘要：

  通过4-氨基-5- [环己基]的环化反应，已经合成了一些6-取代的1,2,4-三唑并[3,4-b] -1,3,4-噻二唑衍生物（4a-f和5a-d）。通过一步反应，将1-（6-甲氧基-2-萘基乙基）-3-巯基-（4H）-1,2,4-三唑（3）与各种取代的芳族酸和芳基/烷基异硫氰酸酯一起使用。通过已知的实验模型，用药理学方法评估目标化合物的抗炎和止痛潜力。其中一些显示出明显的活性。对于有效化合物，观察到极低的致溃疡指数。

  DOI：

  10.1016/j.bmcl.2007.06.003

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
• Naproxen in heterocyclic chemistry: Novel syntheses of triazoles, triazolothiadiazines, triazolothiadiazoles, and triazolothiadiazepine bearing an asymmetric carbon atom and radiostability of the biologically active compounds
  作者：Y. A. Ammar、M. M. Ghorab、A. M. Sh. El-Sharief、Sh. I. Mohamed

  DOI：10.1002/hc.10019

  日期：——

  synthesized starting from 2-(6-methoxy-2-naphthyl)propanoic acid (1) (Naproxen). The structures of the synthesized compounds were elucidated by elemental analyses and spectral data. Compounds 2, 5, 11, 12, 14, and 15 exhibited a remarkable antifungal activity compared with the standard fungicide Mycostatine. Radiosterilization of the biologically active compounds 2, 5, 11, and 14 in the dry state may prove

  几种s-三唑2、7a、10、12；s-三唑并[3,4-b][1,3,4]噻二嗪(3-5)；s-三唑并[3,4-b][1,3,4]噻二唑（6、8、11、15）；和 s-三唑并 [3,4-b][1,3,4] 噻二氮杂 (14) 从 2-(6-甲氧基-2-萘基) 丙酸 (1) (萘普生) 开始合成。通过元素分析和光谱数据阐明了合成化合物的结构。与标准杀真菌剂 Mycostatin 相比，化合物 2、5、11、12、14 和 15 表现出显着的抗真菌活性。生物活性化合物 2、5、11 和 14 在干燥状态下的放射灭菌可能证明是适用的（在高达 40 kGy 的情况下保持其结构不变）。© 2002 Wiley Periodicals, Inc. 杂原子化学 13:199–206, 2002; 在线发表于 Wiley Interscience (www.interscience.wiley.com)。DOI
• 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.
• Amir, Mohammad; Oberoi, Antu; Alam, Shah, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 2, p. 237 - 239
  作者：Amir, Mohammad、Oberoi, Antu、Alam, Shah

  DOI：——

  日期：——
• Non-carboxylic analogues of arylpropionic acids: Synthesis, anti-inflammatory activity and ulcerogenic potential
  作者：Kamel A. Metwally、Shada H. Yaseen、El-Sayed M. Lashine、Hassan M. El-Fayomi、Mohamed E. El-Sadek

  DOI：10.1016/j.ejmech.2006.09.001

  日期：2007.2

  Two series of 1,2,4-triazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles derived from three selected arylpropionic acids namely, ibuprofen, flurbiprofen and naproxen, were synthesized and evaluated for anti-inflammatory activity and ulcerogenic potential. All the tested compounds exhibited anti-inflammatory activity comparable to that of hydrocortisone. Compared to ibuprofen, however, all the tested compounds displayed more potent anti-inflammatory activity. Compounds tested for ulcerogenicity showed no or minimal u1cerogenic effect compared to indomethacin. (c) 2006 Elsevier Masson SAS. All rights reserved.