3-(1,3-Benzothiazol-2-yl)-5-bromopyrazin-2-amine | 1286238-61-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 3-(1,3-Benzothiazol-2-yl)-5-bromopyrazin-2-amine
• CAS: 1286238-61-6
• 化学式: C₁₁H₇BrN₄S
• 分子量: 307.173
• InChiKey: FZEPECOFRDCQQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(1,3-Benzothiazol-2-yl)-5-bromopyrazin-2-amine 、 4-（甲磺酰基）苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以38%的产率得到3-(benzo[d]thiazol-2-yl)-5-(4-(methylsulfonyl)phenyl)-pyrazin-2-amine
  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
• 作为产物：
  描述：

  2-氨基苯硫醇 、 3-氨基-2-氰基-6-溴吡嗪 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 生成 3-(1,3-Benzothiazol-2-yl)-5-bromopyrazin-2-amine
  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

• 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。
• COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE FOR THE TREATMENT OF CANCER
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP3311816A1

  公开（公告）日：2018-04-25

  The present invention relates to compounds useful as inhibitors of ATR protein kinase for use in the treatment of a cancer having a defect in the ATM signaling pathway. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of this invention and combination therapies thereof; use of said compounds in the treatment of various diseases, disorders, and conditions; 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. Preferably, the compound is VE-822.

  本发明涉及作为 ATR 蛋白激酶抑制剂用于治疗 ATM 信号通路缺陷癌症的化合物。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及其联合疗法；所述化合物在治疗各种疾病、失调和病症中的用途；制备本发明化合物的工艺；制备本发明化合物的中间体；以及在体外应用中使用本发明化合物的方法，例如研究生物和病理现象中的激酶；研究由此类激酶介导的细胞内信号转导通路；以及比较评估新的激酶抑制剂。 本发明的化合物具有式 I： 其中变量如本文所定义。优选地，本发明化合物为 VE-822。
• PYRAZINE DERIVATIVES USEFUL AS INHIBITORS OF ATR KINASE
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP2376485B1

  公开（公告）日：2017-12-06
• COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE AND COMBINATION THERAPIES THEREOF
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP2833973B1

  公开（公告）日：2017-09-13
• METHOD FOR TREATING CANCER USING A COMBINATION OF CHK1 AND ATR INHIBITORS
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP3157566B1

  公开（公告）日：2019-05-01