2-(3-吡嗪-2-基-1,2,4-恶二唑-5-基)乙肼 | 175203-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-(3-吡嗪-2-基-1,2,4-恶二唑-5-基)乙肼
• 中文别名: 2-(3-吡嗪-2-基-1,2,4-噁二唑-5-基)乙酰肼
• 英文名称: 2-(3-(Pyrazin-2-yl)-1,2,4-oxadiazol-5-yl)acetohydrazide
• 英文别名: 2-(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)acetohydrazide
• CAS: 175203-77-7
• 化学式: C₈H₈N₆O₂
• mdl: MFCD00219748
• 分子量: 220.191
• InChiKey: OBZQEORKTFGMFT-UHFFFAOYSA-N

物化性质

• 熔点：
  184 °C
• 密度：
  1.440±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S24/25
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-Isothiocyanatobutylcyclohexane 、 2-(3-吡嗪-2-基-1,2,4-恶二唑-5-基)乙肼 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 4-(cyclohexylbutyl)-1-(3-pyrazin-2-yl-[1,2,4]oxadiazol-5-yl-acetyl)-thiosemicarbazide
  参考文献：
  名称：

  Aggrecanase-2 inhibitors based on the acylthiosemicarbazide zinc-binding group

  摘要：

  Osteoarthritis is a disabling disease characterized by the articular cartilage breakdown. Aggrecanases are potential therapeutic targets for the treatment of this pathology. At the starting point of this project, an acylthiosemicarbazide was discovered to inhibit aggrecanase-2. The acylthiosemicarbazide Zn binding group is also a convenient linker for library synthesis. A focused library of 920 analogs was thus prepared and screened to establish structure-activity relationships. The modification of the acylthiosemicarbazide was also explored. This strategy combining library design and discrete compounds synthesis yielded inhibitor 35, that is highly selective for aggrecanases over a panel of metalloproteases and inhibits the degradation of native fully glycosylated aggrecan. A docking study generated binding conformations explaining the structure activity relationships. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.027

文献信息

• Identification of RAD51–BRCA2 Inhibitors Using <i>N</i>-Acylhydrazone-Based Dynamic Combinatorial Chemistry
  作者：Greta Bagnolini、Beatrice Balboni、Fabrizio Schipani、Dario Gioia、Marina Veronesi、Francesca De Franco、Cansu Kaya、Ravindra P. Jumde、Jose Antonio Ortega、Stefania Girotto、Anna K. H. Hirsch、Marinella Roberti、Andrea Cavalli

  DOI：10.1021/acsmedchemlett.2c00063

  日期：2022.8.11

  applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further 19F NMR experiments

  RAD51 是一种 ATP 依赖性重组酶，由 BRCA2 募集以通过同源重组介导 DNA 双链断裂修复，是一种有吸引力的抗癌药物靶点。在这里，我们首次在 RAD51 上申请了蛋白质模板化的动态组合化学作为命中识别策略。在设计基于N-酰基腙的动态组合文库后，RAD51 显示出明显的模板效应，可扩增 19 个N-酰基腙。通过 ELISA 测定筛选 RAD51-BRCA2 蛋白质-蛋白质相互作用，提供了 10 种微摩尔范围内的抑制剂。进一步的19 F NMR 实验表明，7可以结合 RAD51 并被 BRC4 取代，表明在 BRCA2 的同一结合口袋中存在相互作用。这些结果不仅证明了 ptDCC 可以成功地应用于全长寡聚 RAD51，而且还可以解决对鉴定小分子 PPI 抑制剂的替代策略的需求。
• Hit optimization by dynamic combinatorial chemistry on <i>Streptococcus pneumoniae</i> energy-coupling factor transporter ECF-PanT
  作者：Ioulia Antonia Exapicheidou、Atanaz Shams、Hamza Ibrahim、Aleksei Tsarenko、Michael Backenköhler、Mostafa M. Hamed、Eleonora Diamanti、Andrea Volkamer、Dirk J. Slotboom、Anna K. H. Hirsch

  DOI：10.1039/d3cc04738e

  日期：——

  First application of dynamic combinatorial chemistry to the whole complex of the energy-coupling factor transporter PanT from Streptococcus pneumoniae.

  首次将动态组合化学应用于肺炎链球菌能量偶联因子转运体 PanT 的整个复合物。
• Aggrecanase-2 inhibitors based on the acylthiosemicarbazide zinc-binding group
  作者：Lucie Maingot、Jamal Elbakali、Julie Dumont、Damien Bosc、Nicolas Cousaert、Agathe Urban、Gaelle Deglane、Bruno Villoutreix、Hideaki Nagase、Olivier Sperandio、Florence Leroux、Benoit Deprez、Rebecca Deprez-Poulain

  DOI：10.1016/j.ejmech.2013.08.027

  日期：2013.11

  Osteoarthritis is a disabling disease characterized by the articular cartilage breakdown. Aggrecanases are potential therapeutic targets for the treatment of this pathology. At the starting point of this project, an acylthiosemicarbazide was discovered to inhibit aggrecanase-2. The acylthiosemicarbazide Zn binding group is also a convenient linker for library synthesis. A focused library of 920 analogs was thus prepared and screened to establish structure-activity relationships. The modification of the acylthiosemicarbazide was also explored. This strategy combining library design and discrete compounds synthesis yielded inhibitor 35, that is highly selective for aggrecanases over a panel of metalloproteases and inhibits the degradation of native fully glycosylated aggrecan. A docking study generated binding conformations explaining the structure activity relationships. (C) 2013 Elsevier Masson SAS. All rights reserved.