6-溴-[1,2,4]噻唑并[1,5-a]吡嗪-2-胺 | 1184915-33-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡嗪类
• 中文名称: 6-溴-[1,2,4]噻唑并[1,5-a]吡嗪-2-胺
• 英文名称: 6-bromo-[1,2,4]triazolo[1,5-a]pyrazin-2-amine
• CAS: 1184915-33-0
• 化学式: C₅H₄BrN₅
• 分子量: 214.024
• InChiKey: PNVSGTXSNOHCTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-溴-[1,2,4]噻唑并[1,5-a]吡嗪-2-胺 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三环己基膦 、 三氯化磷 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 生成 C₁₅H₁₅N₅O
  参考文献：
  名称：

  De Novo Design of Protein Kinase Inhibitors by in Silico Identification of Hinge Region-Binding Fragments

  摘要：

  Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discovery. However, the discovery and development of novel inhibitors remains challenging. Here, we describe a structure-based de novo design approach that generates novel, hinge-binding fragments that are synthetically feasible and can be elaborated to small molecule libraries. Starting from commercially available compounds, core fragments were extracted, filtered for pharmacophoric properties compatible with hinge-region binding, and docked into a panel of protein kinases. Fragments with a high consensus score were subsequently short-listed for synthesis. Application of this strategy led to a number of core fragments with no previously reported activity against kinases. Small libraries around the core fragments were synthesized, and representative compounds were tested against a large panel of protein kinases and subjected to co-crystallization experiments. Each of the tested compounds was active against at least one kinase, but not all kinases in the panel were inhibited. A number of compounds showed high ligand efficiencies for therapeutically relevant kinases; among them were MAPKAP-K3, SRPK1, SGK1, TAK1, and GCK for which only few inhibitors are reported in the literature.

  DOI：

  10.1021/cb300729y
• 作为产物：
  描述：

  ethyl [(5-bromopyrazin-2-yl)carbamothioyl]carbamate 在 盐酸羟胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 2.0h， 以46.2 g的产率得到6-溴-[1,2,4]噻唑并[1,5-a]吡嗪-2-胺
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS FOR THE TREATMENT OF CANCER
  [FR] NOUVEAUX COMPOSÉS DESTINÉS AU TRAITEMENT DU CANCER

  摘要：

  本发明涉及一种对Mps-1激酶具有抑制作用的新化合物，涉及制备该化合物的方法，包括该化合物的药物组合物和组合物，以及用于制造治疗或预防疾病的药物组合物的使用，以及在制备该化合物中有用的中间体化合物。

  公开号：

  WO2014198594A1

文献信息

• [EN] BICYCLIC AMINES AS CDK2 INHIBITORS<br/>[FR] AMINES BICYCLIQUES UTILISÉES EN TANT QU'INHIBITEURS DE CDK2
  申请人：INCYTE CORP

  公开号：WO2021072232A1

  公开（公告）日：2021-04-15

  The present application provides bicyclic amines that are inhibitors of cyclin-dependent kinase 2 (CDK2), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

  本申请提供了对细胞周期依赖性激酶2（CDK2）具有抑制作用的双环胺类化合物，以及其药物组合物和使用这些化合物治疗癌症的方法。
• NOVEL COMPOUNDS FOR THE TREATMENT OF CANCER
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160207928A1

  公开（公告）日：2016-07-21

  The present invention relates to novel compounds showing an inhibitory effect on Mps-1 kinase, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及新型化合物，显示对Mps-1激酶具有抑制作用，涉及制备这些化合物的方法，包括这些化合物的制药组合物和组合物，涉及使用这些化合物制造治疗或预防疾病的药物组合物，以及用于制备这些化合物的中间体化合物。
• [EN] NOVEL COMPOUNDS FOR THE TREATMENT OF CANCER<br/>[FR] NOUVEAUX COMPOSÉS DESTINÉS AU TRAITEMENT DU CANCER
  申请人：BAYER PHARMA AG

  公开号：WO2014198594A1

  公开（公告）日：2014-12-18

  The present invention relates to novel compounds showing an inhibitory effect on Mps-1 kinase, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及一种对Mps-1激酶具有抑制作用的新化合物，涉及制备该化合物的方法，包括该化合物的药物组合物和组合物，以及用于制造治疗或预防疾病的药物组合物的使用，以及在制备该化合物中有用的中间体化合物。
• <i>De Novo</i> Design of Protein Kinase Inhibitors by <i>in Silico</i> Identification of Hinge Region-Binding Fragments
  作者：Robert Urich、Grant Wishart、Michael Kiczun、André Richters、Naomi Tidten-Luksch、Daniel Rauh、Brad Sherborne、Paul G. Wyatt、Ruth Brenk

  DOI：10.1021/cb300729y

  日期：2013.5.17

  Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discovery. However, the discovery and development of novel inhibitors remains challenging. Here, we describe a structure-based de novo design approach that generates novel, hinge-binding fragments that are synthetically feasible and can be elaborated to small molecule libraries. Starting from commercially available compounds, core fragments were extracted, filtered for pharmacophoric properties compatible with hinge-region binding, and docked into a panel of protein kinases. Fragments with a high consensus score were subsequently short-listed for synthesis. Application of this strategy led to a number of core fragments with no previously reported activity against kinases. Small libraries around the core fragments were synthesized, and representative compounds were tested against a large panel of protein kinases and subjected to co-crystallization experiments. Each of the tested compounds was active against at least one kinase, but not all kinases in the panel were inhibited. A number of compounds showed high ligand efficiencies for therapeutically relevant kinases; among them were MAPKAP-K3, SRPK1, SGK1, TAK1, and GCK for which only few inhibitors are reported in the literature.