2-phenyl-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one | 20085-45-4

• 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-phenyl-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
• 英文别名: 2-phenyl-5-sulfanylidene-1H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one
• CAS: 20085-45-4
• 化学式: C₁₀H₇N₅OS
• 分子量: 245.264
• InChiKey: ZUGSKXIMHDCKSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-phenyl-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one 、 1-碘代丙烷 在 sodium hydroxide 作用下， 以73.1%的产率得到2-phenyl-5-(propylthio)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one
  参考文献：
  名称：

  Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones

  摘要：

  In our lead finding program, a series of 5-thioxo-[1,2,4] triazolo[1,5-a][1,3,5]triazin-7-ones and their 5-thio- alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2013.07.004
• 作为产物：
  描述：

  3-氨基-5-苯基-1,2,4-三唑 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 2-phenyl-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
  参考文献：
  名称：

  胸苷磷酸化酶抑制活性的合成，体外评估以及1,3,5-triazin-2,4-dione及其融合类似物的计算机模拟研究

  摘要：

  基于与参考化合物的结构相似性，设计，合成了一系列1,3,5-triazin-2,4-dione及其融合类似物，并对其体外胸苷磷酸化酶抑制潜力进行了评估。发现单环类似物是无活性的。在合成的不同稠合衍生物中，在C7 / C4处具有酮基（C = O）和在C5 / C2位置具有硫酮基（C = S）的化合物显示出与阳性对照7-脱氮黄嘌呤（7-DX）相当的TP抑制活性。（IC 50值= 42.63μM）。进行了目标化合物与胸苷磷酸化酶的分子对接，以说明关于合理的配体-酶结合相互作用的重要结构信息。

  DOI：

  10.1007/s00044-013-0589-1

文献信息

• [EN] INHIBITORS OF FATTY ACID BINDING PROTEIN (FABP)<br/>[FR] INHIBITEURS DE LA PROTÉINE DE LIAISON AUX ACIDES GRAS (FABP)
  申请人：SCHERING CORP

  公开号：WO2010056631A1

  公开（公告）日：2010-05-20

  The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein ("FABP") inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the present invention is shown below: (I)

  本发明涉及新型杂环化合物作为脂肪酸结合蛋白（"FABP"）抑制剂，包括该杂环化合物的药物组合物以及利用该化合物治疗或预防心血管疾病、代谢紊乱、肥胖或与肥胖相关的疾病、糖尿病、血脂异常、糖尿病并发症、糖耐量受损或空腹血糖受损的用途。本发明的一个示例化合物如下所示：（I）
• Synthesis, in vitro evaluation of thymidine phosphorylase inhibitory activity, and in silico study of 1,3,5-triazin-2,4-dione and its fused analogues
  作者：Hriday Bera、Wai-Keung Chui、Sayan Dutta Gupta、Anton V. Dolzhenko、Lingyi Sun

  DOI：10.1007/s00044-013-0589-1

  日期：2013.12

  5-triazin-2,4-dione and their fused analogues was designed, synthesized and their in vitro thymidine phosphorylase inhibitory potential was evaluated. The monocyclic analogues were found to be inactive. Among the different fused derivatives synthesized, compounds having keto group (C=O) at C7/C4 and thioketo group (C=S) at C5/C2 position showed TP inhibitory activity comparable to positive control, 7-deazaxanthine

  基于与参考化合物的结构相似性，设计，合成了一系列1,3,5-triazin-2,4-dione及其融合类似物，并对其体外胸苷磷酸化酶抑制潜力进行了评估。发现单环类似物是无活性的。在合成的不同稠合衍生物中，在C7 / C4处具有酮基（C = O）和在C5 / C2位置具有硫酮基（C = S）的化合物显示出与阳性对照7-脱氮黄嘌呤（7-DX）相当的TP抑制活性。（IC 50值= 42.63μM）。进行了目标化合物与胸苷磷酸化酶的分子对接，以说明关于合理的配体-酶结合相互作用的重要结构信息。
• INHIBITORS OF FATTY ACID BINDING PROTEIN (FABP)
  申请人：Shipps, JR. Gerald W.

  公开号：US20110237575A1

  公开（公告）日：2011-09-29

  The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (“FABP”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the present invention is shown below: (I)

  本发明涉及新型杂环化合物作为脂肪酸结合蛋白（“FABP”）抑制剂，包括所述杂环化合物的制药组合物以及用于治疗或预防心血管疾病、代谢紊乱、肥胖或肥胖相关疾病、糖尿病、血脂异常、糖尿病并发症、糖耐量受损或空腹血糖受损的化合物的用途。本发明的一种说明性化合物如下：（I）
• 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
  作者：Hriday Bera、Bee Jen Tan、Lingyi Sun、Anton V. Dolzhenko、Wai-Keung Chui、Gigi Nagar Chee Chiu

  DOI：10.1016/j.ejmech.2013.06.051

  日期：2013.9

  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.
• US8815875B2
  申请人：——

  公开号：US8815875B2

  公开（公告）日：2014-08-26