4-氯-5-异丙基吡咯并[1,2-F][1,2,4]三嗪 | 888720-52-3

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 中文名称: 4-氯-5-异丙基吡咯并[1,2-F][1,2,4]三嗪
• 中文别名: 4-氯-5-异丙基吡咯并[2,1-F]的[1,2,4]三嗪
• 英文名称: 4-chloro-5-isopropylpyrrolo[2,1-f][1,2,4]triazine
• 英文别名: 4-chloro-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazine
• CAS: 888720-52-3
• 化学式: C₉H₁₀ClN₃
• mdl: MFCD11519386
• 分子量: 195.651
• InChiKey: QDBLQKDCZMHEPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  trans-dimethylcyclohexane-1,4-diamine 、 4-氯-5-异丙基吡咯并[1,2-F][1,2,4]三嗪 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 以17%的产率得到trans-N,N-dimethyl-N'-(5-isopropylpyrrolo[2,1-f][1,2,4]triazin-4-yl)-1,4-cyclohexanediamine
  参考文献：
  名称：

  Optimization of permeability in a series of pyrrolotriazine inhibitors of IRAK4

  摘要：

  We have developed a series of orally efficacious IRAK4 inhibitors, based on a scaffold hopping strategy and using rational structure based design. Efforts to tackle low permeability and high efflux in our previously reported pyrrolopyrimidine series (Scott et al., 2017) led to the identification of pyrrolotriazines which contained one less formal hydrogen bond donor and were intrinsically more lipophilic. Further optimisation of substituents on this pyrrolotriazine core culminated with the discovery of 30 as a promising in vivo probe to assess the potential of IRAK4 inhibition for the treatment of MyD88 mutant DLBCL in combination with a BTK inhibitor. When tested in an ABC-DLBCL model with a dual MyD88/CD79 mutation (OCI-LY10), 30 demonstrated tumour regressions in combination with ibrutinib. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.01.008
• 作为产物：
  描述：

  5-Isopropylpyrrolo[2,1-f][1,2,4]triazin-4(1H)-one 、 三氯氧磷 在 氮气 、 乙酸乙酯 、 碳酸氢钠 、 magnesium sulfate 作用下， 反应 1.5h， 生成 4-氯-5-异丙基吡咯并[1,2-F][1,2,4]三嗪
  参考文献：
  名称：

  Fused heterocyclic kinase inhibitors

  摘要：

  通常，本发明涉及公式I和II的化合物，包括其药学上可接受的盐。本发明的化合物可用作蛋白激酶抑制剂，因此可用于治疗癌症和其他蛋白激酶介导的疾病。

  公开号：

  US07439246B2

文献信息

• Pyrrolotriazine kinase inhibitors
  申请人：Borzilleri Robert M.

  公开号：US20060004006A1

  公开（公告）日：2006-01-05

  In general, the instant invention comprises compounds of Formulas I and II including pharmaceutically acceptable salts thereof. The compounds of the invention are useful as protein kinase inhibitors and therefore are useful for treating cancer and other protein kinase mediated diseases.

  一般而言，本发明涉及公式I和II的化合物及其药学上可接受的盐。本发明的化合物可用作蛋白激酶抑制剂，因此可用于治疗癌症和其他蛋白激酶介导的疾病。
• US7173031B2
  申请人：——

  公开号：US7173031B2

  公开（公告）日：2007-02-06
• US7439246B2
  申请人：——

  公开号：US7439246B2

  公开（公告）日：2008-10-21
• Optimization of permeability in a series of pyrrolotriazine inhibitors of IRAK4
  作者：Sébastien L. Degorce、Rana Anjum、Keith S. Dillman、Lisa Drew、Sam D. Groombridge、Christopher T. Halsall、Eva M. Lenz、Nicola A. Lindsay、Michele F. Mayo、Jennifer H. Pink、Graeme R. Robb、James S. Scott、Stephen Stokes、Yafeng Xue

  DOI：10.1016/j.bmc.2018.01.008

  日期：2018.2

  We have developed a series of orally efficacious IRAK4 inhibitors, based on a scaffold hopping strategy and using rational structure based design. Efforts to tackle low permeability and high efflux in our previously reported pyrrolopyrimidine series (Scott et al., 2017) led to the identification of pyrrolotriazines which contained one less formal hydrogen bond donor and were intrinsically more lipophilic. Further optimisation of substituents on this pyrrolotriazine core culminated with the discovery of 30 as a promising in vivo probe to assess the potential of IRAK4 inhibition for the treatment of MyD88 mutant DLBCL in combination with a BTK inhibitor. When tested in an ABC-DLBCL model with a dual MyD88/CD79 mutation (OCI-LY10), 30 demonstrated tumour regressions in combination with ibrutinib. (C) 2018 Elsevier Ltd. All rights reserved.
• Fused heterocyclic kinase inhibitors
  申请人：Borzilleri M. Robert

  公开号：US20050288290A1

  公开（公告）日：2005-12-29

  In general, the instant invention comprises compounds of Formulas I and II including pharmaceutically acceptable salts thereof. The compounds of the invention are useful as protein kinase inhibitors and therefore are useful for treating cancer and other protein kinase mediated diseases.

  一般而言，本发明涉及公式I和II的化合物，包括其药学上可接受的盐。本发明的化合物可用作蛋白激酶抑制剂，因此可用于治疗癌症和其他蛋白激酶介导的疾病。