8-bromo-2-(3,4,5-trimethoxy-phenyl)-quinoxaline | 1092500-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-bromo-2-(3,4,5-trimethoxy-phenyl)-quinoxaline
• 英文别名: 8-bromo-2-(3,4,5-trimethoxyphenyl)quinoxaline
• CAS: 1092500-68-9
• 化学式: C₁₇H₁₅BrN₂O₃
• 分子量: 375.222
• InChiKey: FANOBBJLRQBMQB-UHFFFAOYSA-N

物化性质

• 沸点：
  471.2±45.0 °C(Predicted)
• 密度：
  1.424±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  53.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-bromo-2-(3,4,5-trimethoxy-phenyl)-quinoxaline 、 4-硼苯磺酰胺甲酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 作用下， 以 乙二醇二甲醚 为溶剂， 反应 15.0h， 以71%的产率得到N-methyl-4-[3-(3,4,5-trimethoxy-phenyl)-quinoxalin-5-yl]-benzenesulfonamide
  参考文献：
  名称：

  Design of two new chemotypes for inhibiting the Janus kinase 2 by scaffold morphing

  摘要：

  JAK2 is a target of high interest in chronic myeloproliferative disorders drug research. Starting from a screening hit, two new JAK2 inhibitor chemotypes were designed by scaffold morphing. The prototype compounds of these new series showed nanomolar inhibition of the kinase. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.151
• 作为产物：
  描述：

  8-溴-2-氯喹噁啉 、 3,4,5-三甲氧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以68%的产率得到8-bromo-2-(3,4,5-trimethoxy-phenyl)-quinoxaline
  参考文献：
  名称：

  Design of two new chemotypes for inhibiting the Janus kinase 2 by scaffold morphing

  摘要：

  JAK2 is a target of high interest in chronic myeloproliferative disorders drug research. Starting from a screening hit, two new JAK2 inhibitor chemotypes were designed by scaffold morphing. The prototype compounds of these new series showed nanomolar inhibition of the kinase. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.151

文献信息

• Quinoxaline derivatives as tyrosine kinase activity inhibitors
  申请人：Novartis AG

  公开号：US08193189B2

  公开（公告）日：2012-06-05

  The present invention relates to quinoxaline compound of the formula (I): wherein R1 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R7; R2 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R8; R3, R4, R5 and R6 are each independently hydrogen or R9; and R7, R8 and R9 are each independently selected from organic and inorganic substituents, their use in therapy of diseases, in particular diseases mediated by the tyrosine kinase activity of Janus kinases, including JAK-2 and JAK-3 kinases.

  本发明涉及公式（I）的喹喔啉化合物：其中，R1是碳环或杂环，其中任意一个可以用1、2、3、4或5个R7取代；R2是碳环或杂环，其中任意一个可以用1、2、3、4或5个R8取代；R3、R4、R5和R6各自独立地是氢或R9；而R7、R8和R9各自独立地选自有机和无机取代基，它们用于治疗疾病，特别是由Janus激酶的酪氨酸激酶活性介导的疾病，包括JAK-2和JAK-3激酶。
• Quinoxaline Derivatives as Tyrosine Kinase Activity Inhibitors
  申请人：Gerspacher Marc

  公开号：US20100168062A1

  公开（公告）日：2010-07-01

  The present invention relates to quinoxaline compound of the formula (I): wherein R 1 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R 7 ; R 2 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R 8 ; R 3 , R 4 , R 5 and R 8 are each independently hydrogen or R 9 ; and R 7 , R 8 and R 9 are each independently selected from organic and inorganic substituents, their use in therapy of diseases, in particular diseases mediated by the tyrosine kinase activity of Janus kinases, including JAK-2 and JAK-3 kinases.

  本发明涉及式（I）的喹喔啉化合物：其中R1是碳环或杂环，其中任一可以用1、2、3、4或5个R7取代; R2是碳环或杂环，其中任一可以用1、2、3、4或5个R8取代; R3、R4、R5和R8各自独立地是氢或R9; 而R7、R8和R9各自独立地选自有机和无机取代基，在治疗疾病中的应用，特别是由Janus激酶的酪氨酸激酶活性介导的疾病，包括JAK-2和JAK-3激酶。
• WO2008/148867
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors
  作者：Carole Pissot-Soldermann、Marc Gerspacher、Pascal Furet、Christoph Gaul、Philipp Holzer、Clive McCarthy、Thomas Radimerski、Catherine H. Regnier、Fabienne Baffert、Peter Drueckes、Gisele A. Tavares、Eric Vangrevelinghe、Francesca Blasco、Giorgio Ottaviani、Flavio Ossola、Julien Scesa、Janitha Reetz

  DOI：10.1016/j.bmcl.2010.02.056

  日期：2010.4

  We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation. (C) 2010 Elsevier Ltd. All rights reserved.
• QUINOXALINE DERIVATIVES AS INHIBITORS OF THE TYROSINE KINASE ACTIVITY OF JANUS KINASES
  申请人：Novartis AG

  公开号：EP2155201B1

  公开（公告）日：2012-08-01