tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate | 1232423-98-1

• 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: tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate
• 英文别名: tert-butyl N-(3-ethynyl-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-N-tertbutoxycarbonyl-carbamate；N,N-Di(Boc)-3-ethynyl-5-[4-(isopropylsulfonyl)phenyl]pyrazin-2-amine；tert-butyl N-[3-ethynyl-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 1232423-98-1
• 化学式: C₂₅H₃₁N₃O₆S
• 分子量: 501.604
• InChiKey: JYQCDOZYEPKDKU-UHFFFAOYSA-N

物化性质

• 沸点：
  623.6±65.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 3-[3-[4-[(甲基氨基)甲基]苯基]-5-异恶唑基]-5-[4-[异丙磺酰基]苯基]-2-吡嗪胺
  参考文献：
  名称：

  Rational Design of 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine (VX-970, M6620): Optimization of Intra- and Intermolecular Polar Interactions of a New Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase Inhibitor

  摘要：

  The DNA damage response (DDR) is a DNA damage surveillance and repair mechanism that can limit the effectiveness of radiotherapy and DNA-damaging chemotherapy, commonly used treatment modalities in cancer. Two related kinases, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related kinase (ATR), work together as apical proteins in the DDR to maintain genome stability and cell survival in the face of potentially lethal forms of DNA damage. However, compromised ATM signaling is a common characteristic of tumor cells, which places greater reliance on ATR to mediate the DDR. In such circumstances, ATR inhibition has been shown to enhance the toxicity of DNA damaging chemotherapy to many cancer cells in multiple preclinical studies, while healthy tissue with functional ATM can tolerate ATR inhibition. ATR therefore represents a very attractive anticancer target. Herein we describe the discovery of VX-970/M6620, the first ATR inhibitor to enter clinical studies, which is based on a 2-aminopyrazine core first reported by Charrier et al. (J. Med. Chem. 2011, 54, 2320-2330, DOI: ).

  DOI：

  10.1021/acs.jmedchem.9b00426
• 作为产物：
  描述：

  3-bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine 在 copper(l) iodide 、 四(三苯基膦)钯 4-二甲氨基吡啶 、 水 、 sodium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate
  参考文献：
  名称：

  [EN] COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
  [FR] COMPOSÉS UTILES COMME INHIBITEURS DE LA KINASE ATR

  摘要：

  本发明涉及作为ATR蛋白激酶抑制剂的吡咯并吡嗪化合物。本发明还涉及包含本发明化合物的药用可接受组合物；使用本发明化合物治疗各种疾病、障碍和状况的方法；制备本发明化合物的方法；制备本发明化合物的中间体；以及使用本发明化合物在体外应用中的方法，例如研究生物和病理现象中的激酶；研究由这类激酶介导的细胞内信号转导途径；以及比较评估新的激酶抑制剂。本发明的化合物具有式I，其中变量如本文所述定义。

  公开号：

  WO2012178123A1

文献信息

• [EN] COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE<br/>[FR] COMPOSÉS UTILES EN TANT QU'INHIBITEURS DE L'ATR KINASE
  申请人：VERTEX PHARMA

  公开号：WO2011143399A1

  公开（公告）日：2011-11-17

  The present invention relates to pyrazine and pyridine 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 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.

  本发明涉及用作ATR蛋白激酶抑制剂的吡嗪和吡啶化合物。该发明还涉及包括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、紊乱和症状的方法；制备本发明化合物的方法；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，例如在生物和病理现象中研究激酶、介导这些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式(I)：其中变量如本文所定义。
• [EN] COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE<br/>[FR] COMPOSÉS UTILES COMME INHIBITEURS DE KINASE ATR
  申请人：VERTEX PHARMA

  公开号：WO2013049722A1

  公开（公告）日：2013-04-04

  The present invention relates to 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; solid forms 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-l : wherein the variables are as defined herein. Additionally, the compounds of this invention have formula II: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

  本发明涉及用作ATR蛋白激酶抑制剂的化合物。本发明还涉及包含本发明化合物的药用可接受组合物；使用本发明化合物治疗各种疾病、障碍和状况的方法；制备本发明化合物的方法；本发明化合物的制备中间体；本发明化合物的固体形式；以及使用化合物进行体外应用的方法，例如研究生物和病理现象中的激酶；研究由这类激酶介导的细胞内信号转导途径；以及新激酶抑制剂的比较评估。本发明的化合物具有公式I-l：其中变量如本文所定义。另外，本发明的化合物具有公式II：或其药用可接受的盐，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：US20140107093A1

  公开（公告）日：2014-04-17

  The present invention relates to 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: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

  本发明涉及作为ATR蛋白激酶抑制剂有用的化合物。该发明还涉及包括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、疾病和症状的方法；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。本发明的化合物具有式I：或药学上可接受的盐，其中变量如本文所定义。
• [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。
• [EN] COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE<br/>[FR] COMPOSÉS UTILES EN TANT QU'INHIBITEURS DE KINASE ATR
  申请人：VERTEX PHARMA

  公开号：WO2013049719A1

  公开（公告）日：2013-04-04

  The invention relates to the compound 5-(4-isopropylsulfonylphenyl) -3-[3-[4-[(3R)-morpholin-3-yl]phenyl]isoxazol-5-yl]pyrazine-2-amine and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of ATR kinase.

  该发明涉及化合物5-(4-异丙磺酰基苯基)-3-[3-[4-[(3R)-吗啉-3-基]苯基]异恶唑-5-基]吡嗪-2-胺及其药用可接受的盐。这些化合物可用作ATR激酶的抑制剂。