6-(4-fluorophenyl)-3-(pyridin-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine | 785787-83-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-(4-fluorophenyl)-3-(pyridin-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• 英文别名: 6-(4-fluorophenyl)-3-pyridin-4-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• CAS: 785787-83-9
• 化学式: C₁₅H₁₀FN₅S
• 分子量: 311.342
• InChiKey: PIWOCHFLZWLQSH-UHFFFAOYSA-N

物化性质

• 熔点：
  234-235 °C(Solv: ethanol (64-17-5))
• 沸点：
  543.3±60.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  potassium 4-pyridinyldithiocarbazate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 7.5h， 生成 6-(4-fluorophenyl)-3-(pyridin-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
  参考文献：
  名称：

  Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

  摘要：

  Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure-activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 mu g/mL; MIC-MDRTB = 2.0 mu g/mL; MIC-RDRTB = 0.25 mu g/mL; Mt SD-IC50 = 86.39 mu g/mL; and 6g-3, MIC-H37Rv = 1.0 mu g/mL; MIC-MDRTB = 4.0 mu g/mL; MICRDRTB = 2.0 mu g/mL; Mt SD-IC50 = 73.57 mu g/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance- reversing agents. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.10.027

文献信息

• Synthesis, anti-inflammatory, analgesic, and antibacterial activities of some triazole, triazolothiadiazole, and triazolothiadiazine derivatives
  作者：Mostafa A. Hussein、Refaat M. Shaker、Mohammed A. Ameen、Mohammed F. Mohammed

  DOI：10.1007/s12272-011-0802-z

  日期：2011.8

  of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole 1 with the appropriate aldehyde. Compounds 4a–i were synthesized in a one pot reaction involving compounds 3a–i, formaldehyde, and morpholine. Condensation of compound 1 with the appropriate acids or 4-substituted phenacyl bromide gave compounds 6a–d and 8a–f respectively. The chemical structures of the newly synthesized derivatives were elucidated

  本研究涉及新的 1,2,4-三唑、1,3,4-噻二唑和 1,3,4-噻二嗪衍生物的合成。衍生物 3a–i 是通过 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole 1 与适当的醛缩合获得的。化合物 4a-i 是在涉及化合物 3a-i、甲醛和吗啉的一锅反应中合成的。化合物 1 与适当的酸或 4-取代苯甲酰溴缩合分别得到化合物 6a-d 和 8a-f。使用不同的光谱和元素分析方法阐明了新合成衍生物的化学结构。评估了所有化合物的抗炎活性，并使用吲哚美辛作为参考药物测试了最有效的衍生物的镇痛活性。此外，评估了大多数活性化合物的致溃疡性和 LD50。此外，研究了新合成衍生物的抗菌活性。
• Structural elucidation and in-silico evaluation of 1,2,4-triazole derivative as potent Omicron variant of SARS-CoV-2 spike protein inhibitor with pharmacokinetics ADMET and drug-likeness predictions
  作者：D.C. Vinay Kumar、B.S. Chethan、Shalini V．、K.S. Rangappa、N.K. Lokanath

  DOI：10.1016/j.molstruc.2023.136976

  日期：2024.2

  agreement with theoretical values. The crystal structure is determined using single crystal X-ray diffraction study and the structure is reinforced by several intra-, intermolecular and π···π interactions. These interactions result in the formation of R12(7), R33(17), S(5) and S(6) synthons which significantly contribute towards the stability of the crystal structure. Further, these interactions are validated

  当代医学和药学最重要的问题之一是寻找强大的生物活性、高效、低毒的抗新冠药物。相比之下，目前的工作涉及三唑衍生物 6-(4-氟苯基)-3-(吡啶-4基)-7H-(1,2,4)三唑并(3,4-b) (1,3, 4) 噻二嗪 (FPTT) 及其使用各种光谱技术（LCMS、NMR、UV-vis、FTIR）的表征。对振动波数进行了评估，发现与理论值非常吻合。晶体结构通过单晶 X 射线衍射研究确定，并且该结构通过多种分子内、分子间和π … π相互作用得到增强。这些相互作用导致R 1 2 (7 )、R 3 3 (17)、S(5) 和 S(6) 合成子的形成，这对晶体结构的稳定性有显着贡献。此外，这些相互作用通过赫什菲尔德表面和二维指纹图分析得到验证。CH·N和H·H接触是主要贡献者，与拓扑和自然键轨道结果一致。通过密度泛函理论（DFT）优化的几何参数与实验数据吻合良好。此外，使用优化的结构评估了化合物的
• Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains
  作者：Ziqiang Li、Xiaoguang Bai、Qi Deng、Guoning Zhang、Lei Zhou、Yishuang Liu、Juxian Wang、Yucheng Wang

  DOI：10.1016/j.bmc.2016.10.027

  日期：2017.1

  Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure-activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 mu g/mL; MIC-MDRTB = 2.0 mu g/mL; MIC-RDRTB = 0.25 mu g/mL; Mt SD-IC50 = 86.39 mu g/mL; and 6g-3, MIC-H37Rv = 1.0 mu g/mL; MIC-MDRTB = 4.0 mu g/mL; MICRDRTB = 2.0 mu g/mL; Mt SD-IC50 = 73.57 mu g/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance- reversing agents. (C) 2016 Elsevier Ltd. All rights reserved.