anilide of 3-aminopyrazinecarboxylic acid | 36204-80-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: anilide of 3-aminopyrazinecarboxylic acid
• 英文别名: 3-amino-N-phenylpyrazine-2-carboxamide；3-amino-pyrazine-2-carboxylic acid anilide；3-Amino-pyrazin-2-carbonsaeure-anilid
• CAS: 36204-80-5
• 化学式: C₁₁H₁₀N₄O
• mdl: MFCD17879633
• 分子量: 214.227
• InChiKey: AUTGTAZMHHRJAB-UHFFFAOYSA-N

物化性质

• 熔点：
  106-107 °C(Solv: ethanol (64-17-5))
• 沸点：
  345.4±42.0 °C(Predicted)
• 密度：
  1.364±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基吡嗪-2-羧酸甲酯 在 氰基磷酸二乙酯 、 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 4.0h， 生成 anilide of 3-aminopyrazinecarboxylic acid
  参考文献：
  名称：

  Discovery of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3 Related (ATR) Protein Kinase as Potential Anticancer Agents

  摘要：

  DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA. ATR is a major regulator of the DDR and an attractive anticancer target. Herein, we describe the discovery of a series of aminopyrazines with potent and selective ATR inhibition. Compound 45 inhibits ATR with a K-i of 6 nM, shows >600-fold selectivity over related kinases ATM or DNA-PK, and blocks ATR signaling in cells with an IC50 of 0.42 mu M. Using this compound, we show that ATR inhibition markedly enhances death induced by DNA-damaging agents in certain cancers but not normal cells. This differential response between cancer and normal cells highlights the great potential for ATR inhibition as a novel mechanism to dramatically increase the efficacy of many established drugs and ionizing radiation.

  DOI：

  10.1021/jm101488z

文献信息

• Derivatives of 3-Aminopyrazine-2-carboxamides: Synthesis, Antimicrobial Evaluation, and in Vitro Cytotoxicity
  作者：Ghada Bouz、Lucia Semelková、Ondřej Janďourek、Klára Konečná、Pavla Paterová、Lucie Navrátilová、Vladimír Kubíček、Jiří Kuneš、Martin Doležal、Jan Zitko

  DOI：10.3390/molecules24071212

  日期：——

  We report the design, synthesis, and in vitro antimicrobial activity of a series of N-substituted 3-aminopyrazine-2-carboxamides with free amino groups in position 3 on the pyrazine ring. Based on various substituents on the carboxamidic moiety, the series is subdivided into benzyl, alkyl, and phenyl derivatives. The three-dimensional structures of the title compounds were predicted using energy minimization

  我们报告了一系列 N-取代 3-氨基吡嗪-2-甲酰胺的设计、合成和体外抗菌活性，在吡嗪环上的 3 位具有游离氨基。根据羧酰胺部分上的各种取代基，该系列可细分为苄基、烷基和苯基衍生物。在 AMBER10:EHT 力场下使用能量最小化和低模式分子动力学预测标题化合物的三维结构。在体外评估化合物的抗分枝杆菌、抗菌和抗真菌活性。对结核分枝杆菌 H37Rv (Mtb) 最具活性的化合物是 3-氨基-N-（2,4-二甲氧基苯基）吡嗪-2-甲酰胺（17，MIC = 12.5 µg/mL，46 µM）。对 Mtb 和 M. 的抗分枝杆菌活性。随着碳侧链长度的增加，kansasii 以及烷基衍生物中的抗菌活性增加。对苯基和烷基衍生物观察到抗菌活性，但对苄基衍生物没有观察到。在所有结构亚型中均观察到抗真菌活性，主要针对叉指毛癣菌和白色念珠菌。评估了四种最活跃的化合物（化合物 10、16、17、20）在 HepG2
• Pteridines. XVI. A Synthesis of 2-Aminopyrazine-3-carboxamides by Reductive Ring Cleavage of 3-Hydroxy-1-pyrazolo [b] pyrazines^1-3
  作者：E. C. Taylor、J. W. Barton、T. S. Osdene

  DOI：10.1021/ja01535a045

  日期：1958.1
• LUBOCH, E.;BIERNAT, J. F., POL. J. CHEM., 1981, 55, N 10, 2183-2191
  作者：LUBOCH, E.、BIERNAT, J. F.

  DOI：——

  日期：——
• Discovery of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3 Related (ATR) Protein Kinase as Potential Anticancer Agents
  作者：Jean-Damien Charrier、Steven J. Durrant、Julian M. C. Golec、David P. Kay、Ronald M. A. Knegtel、Somhairle MacCormick、Michael Mortimore、Michael E. O'Donnell、Joanne L. Pinder、Philip M. Reaper、Alistair P. Rutherford、Paul S. H. Wang、Stephen C. Young、John R. Pollard

  DOI：10.1021/jm101488z

  日期：2011.4.14

  DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA. ATR is a major regulator of the DDR and an attractive anticancer target. Herein, we describe the discovery of a series of aminopyrazines with potent and selective ATR inhibition. Compound 45 inhibits ATR with a K-i of 6 nM, shows >600-fold selectivity over related kinases ATM or DNA-PK, and blocks ATR signaling in cells with an IC50 of 0.42 mu M. Using this compound, we show that ATR inhibition markedly enhances death induced by DNA-damaging agents in certain cancers but not normal cells. This differential response between cancer and normal cells highlights the great potential for ATR inhibition as a novel mechanism to dramatically increase the efficacy of many established drugs and ionizing radiation.