2-(4-bromo-3-methyl-phenyl)-5-thioxo-5,6-dihydro-4H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one | 1456613-90-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-bromo-3-methyl-phenyl)-5-thioxo-5,6-dihydro-4H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one
• 英文别名: 2-(4-bromo-3-methylphenyl)-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one；2-(4-bromo-3-methylphenyl)-5-sulfanylidene-1H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one
• CAS: 1456613-90-3
• 化学式: C₁₁H₈BrN₅OS
• 分子量: 338.187
• InChiKey: KVEUPOJZRTUXSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-溴-3-甲基苯甲酰氯 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.66h， 生成 2-(4-bromo-3-methyl-phenyl)-5-thioxo-5,6-dihydro-4H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one
  参考文献：
  名称：

  A structure–activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities

  摘要：

  Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the 5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying degree of inhibitory activity towards thymidine phosphorylase, comparable or better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory mechanism in the presence of variable concentrations of thymidine (dThd). In addition, selected compounds were found to have a noticeable inhibitory effect on the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231 breast cancer cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.051

文献信息

• Synthesis and<i>in vitro</i>Evaluation of 1,2,4-Triazolo[1,5-<i>a</i>][1,3,5]triazine Derivatives as Thymidine Phosphorylase Inhibitors
  作者：Hriday Bera、Anton V. Dolzhenko、Lingyi Sun、Sayan Dutta Gupta、Wai-Keung Chui

  DOI：10.1111/cbdd.12171

  日期：2013.9

  In our lead finding program, a series of 1,2,4‐triazolo[1,5‐a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positions showed varying degrees of TP inhibitory activity comparable with positive control, 7‐deazaxanthine (7‐DX, 2) (IC50 value = 42.63 μm). Enzyme inhibition kinetics study suggested that compound IVn behaved as a mixed‐type inhibitor of the enzyme with respect to thymidine (dThd) as a variable substrate. Compound IVn was also found to inhibit PMA‐induced MMP‐9 expression in MDA‐MB‐231 cells at sublethal concentrations. Computational docking study was performed to illustrate the enzyme inhibition kinetics and to explore the ligand–enzyme interactions.