methyl 3-amino-6-(4-(methylsulfonyl)phenyl)pyrazine-2-carboxylate | 1232423-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: methyl 3-amino-6-(4-(methylsulfonyl)phenyl)pyrazine-2-carboxylate
• 英文别名: methyl 3-amino-6-(4-methylsulfonylphenyl)pyrazine-2-carboxylate
• CAS: 1232423-27-6
• 化学式: C₁₃H₁₃N₃O₄S
• 分子量: 307.33
• InChiKey: KLJOKZQCUUQBGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 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：
  121
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-6-(4-(methylsulfonyl)phenyl)pyrazine-2-carboxylate 在 氰基磷酸二乙酯 、 水 、 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 乙二醇二甲醚 为溶剂， 反应 20.0h， 生成 3-氨基-6-[4-(甲基磺酰基)苯基]-N-苯基-2-吡嗪甲酰胺
  参考文献：
  名称：

  [EN] COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
  [FR] COMPOSÉS UTILISABLES EN TANT QU'INHIBITEURS DE LA KINASE ATR

  摘要：

  公开号：

  WO2011143425A3
• 作为产物：
  描述：

  3-氨基-6-溴吡嗪-2-甲酸甲酯 、 4-（甲磺酰基）苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 cesium fluoride 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以9.3%的产率得到methyl 3-amino-6-(4-(methylsulfonyl)phenyl)pyrazine-2-carboxylate
  参考文献：
  名称：

  [EN] STRAD-BINDING AGENTS AND USES THEREOF
  [FR] AGENTS DE LIAISON À STRAD ET LEURS UTILISATIONS

  摘要：

  披露的内容包括，但不限于，用于结合STRAD假激酶的化合物及其用途。

  公开号：

  WO2021155004A1

文献信息

• Evaluation of [ 18 F]-ATRi as PET tracer for in vivo imaging of ATR in mouse models of brain cancer
  作者：Giuseppe Carlucci、Brandon Carney、Ahmad Sadique、Axel Vansteene、Jun Tang、Thomas Reiner

  DOI：10.1016/j.nucmedbio.2017.01.002

  日期：2017.5

  cell lines and ex vivo biodistribution were performed in subcutaneous U251 MG xenograft bearing athymic nude mice following microPET imaging. RESULTS [18F]-ATRi has a similar pharmacokinetic profile to that of Ve-821. Using an U251 MG glioblastoma mouse model, we evaluated the in vivo binding efficiency of [18F]-ATRi. Blood and tumor showed a statistically significant difference between mice injected

  发生共济失调的毛细血管扩张症和Rad3相关（ATR）苏氨酸丝氨酸激酶是协调DNA损伤反应（DDR）的关键因素之一。因此，抑制ATR可以放大化学疗法和放射疗法的效果，并且几种ATR抑制剂（ATRi）已经在癌症中进行了临床测试。为了更准确地选择患者，进行监测和分期，对ATR进行实时体内成像可能是无价的。合适的显像剂的开发仍然是主要的挑战。方法3-氨基-N-（4- [18F]苯基）-6-（4-（甲基磺酰基）苯基）吡嗪-2-羧酰胺（[18F] -ATRi），与Ve-821的相似类似物（临床与已经建立的合成程序类似，可以轻松完成ATRi候选程序）。在结构上，将18 F引入Ve-821芳香环的4位以生成标记的ATR抑制剂。在microPET成像后，在U251 MG胶质母细胞瘤细胞系中进行了体外实验，并在携带无胸腺裸鼠的皮下U251 MG异种移植物中进行了离体生物分布。结果[18F] -ATRi具有与V
• [EN] PYRAZINE DERIVATIVES USEFUL AS INHIBITORS OF ATR KINASE<br/>[FR] DÉRIVÉS PYRAZINES UTILES EN TANT QU'INHIBITEURS D'ATR KINASE
  申请人：VERTEX PHARMA

  公开号：WO2010071837A1

  公开（公告）日：2010-06-24

  The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula (I):wherein the variables are as defined herein.

  本发明涉及对ATR蛋白激酶具有抑制作用的吡嗪化合物。该发明还涉及包括本发明的化合物的药用可接受组合物；使用本发明的化合物治疗各种疾病、紊乱和症状的方法；制备本发明的化合物的方法；用于制备本发明的化合物的中间体；以及在体外应用中使用化合物的方法，例如在生物和病理现象中研究激酶、介导激酶的细胞内信号传导途径的研究以及新激酶抑制剂的比较评估。本发明的化合物具有如下式(I)的结构，其中变量如本文所定义。
• COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20160311809A1

  公开（公告）日：2016-10-27

  The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

  本发明涉及一种吡嗪化合物，可用作ATR蛋白激酶的抑制剂。本发明还涉及包含本发明化合物的药学上可接受的组合物；使用本发明化合物治疗各种疾病、疾病和病状的方法；制备本发明化合物的方法；用于制备本发明化合物的中间体；以及在体外应用中使用化合物的方法，例如研究生物和病理现象中的激酶，介导这些激酶的细胞内信号转导途径的研究以及新激酶抑制剂的比较评估。本发明化合物具有式I，其中变量如本文所定义。
• Pyrazin-2-amines useful as inhibitors of ATR kinase
  申请人：Charrier Jean-Damien

  公开号：US08841308B2

  公开（公告）日：2014-09-23

  The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

  本发明涉及一种用作ATR蛋白激酶抑制剂的吡嗪化合物。本发明还涉及包含本发明化合物的药学上可接受的组合物；使用本发明化合物治疗各种疾病、疾病和病况的方法；制备本发明化合物的过程；制备本发明化合物的中间体；以及在体外应用中使用化合物的方法，例如研究生物和病理现象中的激酶，介导这些激酶的细胞内信号转导途径的研究以及新激酶抑制剂的比较评估。本发明化合物具有公式I：其中变量如本文所定义。
• Substituted pyrazin-2-amines as inhibitors of ATR kinase
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US09365557B2

  公开（公告）日：2016-06-14

  The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. Certain compounds of this invention have formula IA: wherein the variables are as defined herein.

  本发明涉及吡嗪化合物，其可用作ATR蛋白激酶的抑制剂。本发明还涉及包含本发明化合物的药学上可接受的组合物；使用本发明化合物治疗各种疾病、疾病和病况的方法；制备本发明化合物的过程；用于制备本发明化合物的中间体；以及在体外应用中使用化合物的方法，例如研究生物和病理现象中的激酶、介导这些激酶的细胞内信号转导途径的研究以及新激酶抑制剂的比较评估。本发明的某些化合物具有式IA：其中变量如本文所定义。