5,6-bis(4-fluorophenyl)-1,2,4-triazine-3-thiol | 59663-51-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 5,6-bis(4-fluorophenyl)-1,2,4-triazine-3-thiol
• 英文别名: 5,6-bis(4-fluorophenyl)-3-mercapto-1,2,4-triazine；5,6-bis-(4-fluoro-phenyl)-2(4)H-[1,2,4]triazine-3-thione；3-mercapto-5,6-bis(4-fluorophenyl)-1,2,4-triazine；5,6-bis(4-fluorophenyl)-2H-1,2,4-triazine-3-thione
• CAS: 59663-51-3
• 化学式: C₁₅H₉F₂N₃S
• mdl: MFCD03018186
• 分子量: 301.319
• InChiKey: DLDBGTWAPXNUNC-UHFFFAOYSA-N

物化性质

• 沸点：
  390.3±52.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 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：
  68.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氯甲基吡啶盐酸盐 、 5,6-bis(4-fluorophenyl)-1,2,4-triazine-3-thiol 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 5,6-bis(4-fluorophenyl)-3-(pyridin-3-ylmethylthio)-1,2,4-triazine
  参考文献：
  名称：

  Anticonvulsant activity of 1,2,4-triazine derivatives with pyridyl side chain: synthesis, biological, and computational study

  摘要：

  A series of 5,6-bisaryl-1,2,4-triazine-3-thiol-substituted derivatives were synthesized by condensation of 1,2-diketones and thiosemicarbazide under microwave irradiations and subsequent alkylation of thiol group by chloromethylpyridinium chloride. Evaluation of anticonvulsant activity of compounds was performed by maximal electroshock and pentylenetetrazole-induced seizures tests. In order to evaluate their neuroprotective potential, the ability of compounds to inhibit soybean 15-lipoxygenase was also assessed. Further molecular modeling and docking study on Na+ channel and GABA(A) receptor was performed to elucidate their mechanisms of action and necessary interactions in the active site. Compounds 2c and 2d with bis(4-bromophenyl) and pyridyl substituents showed highest protection up to 70 and 80 % in PTZ and MES-induced seizures, respectively, compared to the control group. Molecular docking study revealed their possible antiseizure mechanism of action through GABA(A) receptor, and in silico assessment of their BBB permeability indicated them as CNS active agents.

  DOI：

  10.1007/s00044-014-1315-3
• 作为产物：
  描述：

  4,4'-二氟安息香 在 硝酸铵 、 copper(II) acetate monohydrate 、 溶剂黄146 作用下， 反应 4.5h， 生成 5,6-bis(4-fluorophenyl)-1,2,4-triazine-3-thiol
  参考文献：
  名称：

  带有咔唑部分的新型1,2,4-三嗪衍生物作为有效的α-葡萄糖苷酶抑制剂的合成和生物学评估。

  摘要：

  设计，合成了一系列新的带有咔唑部分7a-7p的1,2,4-三嗪衍生物，并评估了其对α-葡萄糖苷酶的抑制活性。与标准药物阿卡波糖相比，大多数被筛选的化合物显示出有效的α-葡萄糖苷酶抑制活性，IC50值在4.27±0.07-47.75±0.25μM范围内。在该系列中，化合物7k表现出最强的α-葡萄糖苷酶抑制活性，IC50值为4.27±0.07μM。动力学分析表明，化合物7k是一种非竞争性抑制剂，Ki为4.43μM。此外，通过分子对接证实了化合物7k与α-葡糖苷酶的结合相互作用。这项研究表明，这些带有咔唑部分的1,2,4-三嗪衍生物是一类新型的α-葡萄糖苷酶抑制剂。

  DOI：

  10.1016/j.bmcl.2016.04.071

文献信息

• Synthesis, biological evaluation, and docking studies of novel 5,6-diaryl-1,2,4-triazine thiazole derivatives as a new class of α-glucosidase inhibitors
  作者：Guangcheng Wang、Zhiyun Peng、Zipeng Gong、Yongjun Li

  DOI：10.1016/j.bioorg.2018.03.015

  日期：2018.8

  A novel 5,6-diaryl-1,2,4-triazine thiazole derivatives (7a-7q) were synthesized and characterized by 1H NMR and 13C NMR and evaluated for their α-glucosidase inhibitory activity. All tested compounds displayed good α-glucosidase inhibitory activity with IC50 values ranging between 2.85 ± 0.13 and 14.19 ± 0.23 μM when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Compound 7i (IC50 = 2

  合成了新颖的5,6-二芳基-1,2,4-三嗪噻唑衍生物（7a - 7q），并通过1 H NMR和13 C NMR对其进行了表征，并评估了其对α-葡萄糖苷酶的抑制活性。与标准阿卡波糖（IC 50  = 817.38±6.27μM）相比，所有测试化合物均显示出良好的α-葡萄糖苷酶抑制活性，IC 50值在2.85±0.13和14.19± 0.23μM之间。化合物7i（IC 50 = 2.85±0.13μM）在这一系列化合物中表现出最高的活性。为了研究这类化合物与α-葡萄糖苷酶的结合方式，进行了分子对接研究。该研究表明，这些5,6-二芳基-1,2,4-三嗪噻唑衍生物是一类新的α-葡萄糖苷酶抑制剂。
• 5,6-Diaryl-1,2,4-triazines as topically-active anti-inflammatory agents
  申请人：Eli Lilly and Company

  公开号：US04018923A1

  公开（公告）日：1977-04-19

  A method of treating inflammation which utilizes topically-active 5,6-diaryl-1,2,4-triazines having the formula, ##STR1## wherein R is hydrogen or --(X).sub.n R.sub.1, in which X is either O or S, n is an integer which is either 0 or 1, and R.sub.1 is C.sub.1 -C.sub.8 alkyl, C.sub.7 -C.sub.8 aralkyl, C.sub.3 -C.sub.8 cycloalkyl, or C.sub.4 -C.sub.8 (cycloalkyl)alkyl; and R.sub.2 and R.sub.3 independently are halo, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy, or di(C.sub.1 -C.sub.3 alkyl)amino, with the proviso that at least one of R.sub.2 and R.sub.3 is halo or C.sub.1 -C.sub.3 alkyl; and the pharmaceutically-acceptable acid addition salts of basic members thereof.

  一种治疗炎症的方法，利用具有以下化学式的局部活性的5,6-二芳基-1,2,4-三嗪：其中R为氢或--(X).sub.n R.sub.1，其中X为O或S，n为0或1的整数，R.sub.1为C.sub.1 -C.sub.8烷基，C.sub.7 -C.sub.8芳基烷基，C.sub.3 -C.sub.8环烷基，或C.sub.4 -C.sub.8(环烷基)烷基；R.sub.2和R.sub.3独立地为卤素、C.sub.1 -C.sub.3烷基、C.sub.1 -C.sub.3烷氧基或二(C.sub.1 -C.sub.3烷基)氨基，但R.sub.2和R.sub.3中至少有一个为卤素或C.sub.1 -C.sub.3烷基；以及其药学上可接受的酸盐。
• 5,6-DIARYL-1,2,4-TRIAZINES
  申请人：Eli Lilly and Company

  公开号：US04013654A1

  公开（公告）日：1977-03-22

  5,6-Diaryl-1,2,4-triazines, topically-active anti-inflammatory agents, having the formula, ##STR1## wherein R is hydrogen or --(X).sub.n R.sub.1, in which X is either O or S, n is an integer which is either 0 or 1, and R.sub.1 is C.sub.1 -C.sub.8 alkyl, C.sub.7 -C.sub.8 aralkyl, C.sub.3 -C.sub.8 cycloalkyl, or C.sub.4 -C.sub.8 (cycloalkyl)alkyl; and R.sub.2 and R.sub.3 independently are halo, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy, or di(C.sub.1 -C.sub.3 alkyl)amino, with the proviso that at least one of R.sub.2 and R.sub.3 is halo or C.sub.1 -C.sub.3 alkyl; and the pharmaceutically-acceptable acid addition salts of basic members thereof.

  5,6-二芳基-1,2,4-三嗪是一种具有局部活性的抗炎药物，其化学式为##STR1##其中R为氢或--(X).sub.n R.sub.1，其中X为氧或硫，n是0或1的整数，R.sub.1为C.sub.1-C.sub.8烷基，C.sub.7-C.sub.8芳基烷基，C.sub.3-C.sub.8环烷基或C.sub.4-C.sub.8(环烷基)烷基；R.sub.2和R.sub.3独立地为卤素，C.sub.1-C.sub.3烷基，C.sub.1-C.sub.3烷氧基或二(C.sub.1-C.sub.3烷基)氨基，但R.sub.2和R.sub.3中至少有一个为卤素或C.sub.1-C.sub.3烷基；以及其药用可接受的酸盐。
• 3-Amino-5,6-diaryl-1,2,4-triazines
  申请人：Eli Lilly and Company

  公开号：US03948894A1

  公开（公告）日：1976-04-06

  This invention relates to certain 3-amino-5,6-diaryl-1,2,4-triazines useful as anti-inflammatory agents and a method of treating inflammation.

  这项发明涉及某些3-氨基-5,6-二芳基-1,2,4-三嗪，可用作抗炎药物，并提供了一种治疗炎症的方法。
• Synthesis Novel Fluorinated Cyclic Nanomeric Aza Crown Macrocyclic System Containing 1,2,4-triazine moiety and Ru-complex as Cyclin-dependent kinase 2 (CDK2) inhibitors of tumor cells (Protection of DNA Damage)-Part II
  作者：Wafa A. Bawazir、Reda M. Abdel -Rahman

  DOI：10.13005/ojc/360614

  日期：2020.12.31

  reacted with RuCl3.xH2O to produce the target 7. Structures of the products deduced from their elemental analysis and spectral measurements. Compounds 3, 4, 6, and 7 were evaluated as CDK2 inhibitors of tumor cells; these compounds exhibited a potential activity against CDK2, where the IC50 values were 4.5, 6.8, 4.0, and 5.0 μM respectively in comparison with Olomoucine standard (IC50=5.0 μM).

  从5,6-双（4-氟苯基）-1,2,4-三嗪-之间的相互作用获得了新型氟化的1,5-二取代-1,3,5-三氮杂-6,7-二酮（4）将3-硫醇（1）与2,6-二氨基吡啶2进行反应，然后与草酸二乙酯进行闭环反应。同样，将化合物1与6-（4-氟苯基）-1,2,4-三嗪-3,5-二胺（5）回流得到的Ru-络合物7生成化合物6，然后使后者与RuCl3.xH2O反应。产生目标7。从产品的元素分析和光谱测量得出的产品结构。化合物3、4、6和7被评估为肿瘤细胞的CDK2抑制剂。这些化合物显示出对CDK2的潜在活性，与Olomoucine标准品（IC50 = 5.0μM）相比，IC50值分别为4.5、6.8、4.0和5.0μM。