N-Carbethoxy-N'-(5-phenylpyrazol-3-yl) thioharnstoff | 58095-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-Carbethoxy-N'-(5-phenylpyrazol-3-yl) thioharnstoff
• 英文别名: 4-(5-phenyl-1(2)H-pyrazole-3-yl)-3-thio-allophanic acid ethyl ester；ethyl N-[(5-phenyl-1H-pyrazol-3-yl)carbamothioyl]carbamate
• CAS: 58095-83-3
• 化学式: C₁₃H₁₄N₄O₂S
• 分子量: 290.346
• InChiKey: DPTUTTVIGVRFDV-UHFFFAOYSA-N

物化性质

• 熔点：
  195-196 °C(Solv: benzene (71-43-2))
• 密度：
  1.366±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Carbethoxy-N'-(5-phenylpyrazol-3-yl) thioharnstoff 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.33h， 以71%的产率得到7-phenyl-2-thioxo-2,3-dihydro-1H-pyrazolo[1,5-a][1,3,5]triazin-4-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
• 作为产物：
  描述：

  苯甲酰乙腈 在 hydrazine hydrate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-Carbethoxy-N'-(5-phenylpyrazol-3-yl) thioharnstoff
  参考文献：
  名称：

  Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II

  摘要：

  In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.063

文献信息

• Synthesis of pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors of thymidine phosphorylase
  作者：Lingyi Sun、Hriday Bera、Wai Keung Chui

  DOI：10.1016/j.ejmech.2013.03.063

  日期：2013.7

  evaluate whether pyrazolo[1,5-a][1,3,5]triazin-2,4-diones and pyrazolo[1,5-a][1,3,5]triazin-2-thioxo-4-ones would exhibit TP inhibitory activity. The pyrazolo[1,5-a][1,3,5]triazine nucleus was constructed using a reaction that annulated the 1,3,5-triazine ring onto a pyrazole scaffold. Among the 52 compounds synthesized and tested, it was found that 1,3-dihydro-pyrazolo[1,5-a][1,3,5]triazin-2-thioxo-4-ones

  胸苷磷酸化酶（TP）是一种促进肿瘤生长和转移的酶，因此是有吸引力的可药物治疗靶标。使用已报道的TP抑制剂7-脱氮黄嘌呤（7DX）作为先导化合物；进行这项研究是为了评估吡唑并[1,5- a ] [1,3,5]三嗪-2,4-二酮和吡唑并[1,5- a ] [1,3,5]三嗪-2- thioxo-4-ones将表现出TP抑制活性。吡唑并[1,5- a ] [1,3,5]三嗪核是通过将1,3,5-三嗪环环化到吡唑支架上的反应构建的。在合成和测试的52种化合物中，发现1,3-二氢-吡唑并[1,5- a ] [1,3,5] triazin-2-thioxo-4-ones对TP表现出不同程度的抑制活性。 。最好的化合物17p带有对位取代的五氟硫基的，其IC 50值为0.04μM， 在相同的生物测定条件下，其效价是7DX（IC 50 = 32μM）的800倍左右。研究结果表明，在吡唑并[1,5- a ] [1
• Novel Solution- and Solid-Phase Syntheses of Heterocyclic Systems
  作者：Gaelle Cabon、Berangere Gaucher、Aline Gegout、Sophie Heulle、Thierry Masquelin

  DOI：10.2533/000942903777679280

  日期：——

  Heterocyclic compounds are an attractive source of screening library structures because they possess varied structural diversity and can exhibit potent biological activity. In this context, we present some of our new and versatile approaches to rapid and efficient syntheses of pharmacologically relevant core structures. These include: combination of both solution- and solid-phase processes in the synthesis of pyrazolo[1,5-a]-[1,3,5]-triazin-4-ones and pyrazolo[1,5-a]-[1,3,5]-triazines; parallel, multi-generation synthesis of highly functionalized heterocyclic compounds in solution; a multi-step synthesis of 2,5-diketopiperazine on solid support taking advantage of a bicyclic ?-lactam scaffold, and a combined solid- and solution-phase synthesis of a new class of 2,4-diaminothiazoles.

  杂环化合物是筛选库结构的有吸引力的来源，因为它们具有多样的结构多样性并且可能表现出强大的生物活性。在这个背景下，我们提出了一些新的和多功能的方法，用于快速、高效地合成药理学相关的核心结构。这些方法包括：在合成吡唑并[1,5-a]-[1,3,5]-三唑酮和吡唑并[1,5-a]-[1,3,5]-三嗪时结合溶液相和固相过程；在溶液中并行、多代合成高度官能化的杂环化合物；利用双环β-内酰胺支架在固相上多步合成2,5-二酮哌嗪；以及结合固相和溶液相合成一类新的2,4-二氨基噻唑化合物。
• 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。
• Pyrazolopyrimidine and pyrazolotriazine derivatives and pharmaceutical compositions containing them
  申请人：Gudmundsson Kristjan

  公开号：US20050124616A1

  公开（公告）日：2005-06-09

  The present invention provides compounds of formula (I): pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

  本发明提供了式(I)的化合物：含有该化合物的药物组合物，制备该化合物的方法以及它们作为药物制剂的使用。
• Pyrazolopyrimidine and Pyrazolotriazine Derivatives and Pharmaceutical Compositions Containing Them
  申请人：Gudmundsson Kristjan

  公开号：US20070232623A1

  公开（公告）日：2007-10-04

  The present invention provides compounds of formula (I): pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

  本发明提供了式(I)化合物：包含它们的药物组合物、制备它们的方法以及它们作为药物代理的用途。