[1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-[5-(4-methanesulfonyl-[1,4]diazepan-1-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: [1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-[5-(4-methanesulfonyl-[1,4]diazepan-1-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-amine
• 英文别名: N-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-5-[(4-methylsulfonyl-1,4-diazepan-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine
• 化学式: C₂₇H₂₉FN₈O₂S
• 分子量: 548.644
• InChiKey: XHEGSRSQWOQKMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-(bromomethyl)-4-chloropyrrolo[2,1-f][1,2,4]triazine 在 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 氯仿 、 1,2-二氯乙烷 、 正丁醇 为溶剂， 反应 6.5h， 生成 [1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-[5-(4-methanesulfonyl-[1,4]diazepan-1-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-amine
  参考文献：
  名称：

  Novel C-5 aminomethyl pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  Novel C-5 aminomethyl pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.050

文献信息

• C-5 Modified indazolylpyrrolotriazines
  申请人：——

  公开号：US20030186983A1

  公开（公告）日：2003-10-02

  The present invention provides compounds of formula I 1 and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了I1式化合物及其药用可接受的盐。公式I化合物抑制生长因子受体如HER1、HER2和HER4的酪氨酸激酶活性，因此使它们可用作抗增殖剂。公式I化合物还可用于治疗与通过生长因子受体进行信号转导途径相关的其他疾病。
• C5-modified indazolylpyrrolotriazines
  申请人：Bristol-Myers Squibb Company

  公开号：EP1446401B1

  公开（公告）日：2011-09-14
• US6908916B2
  申请人：——

  公开号：US6908916B2

  公开（公告）日：2005-06-21
• Novel C-5 aminomethyl pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
  作者：Harold Mastalerz、Ming Chang、Ashvinikumar Gavai、Walter Johnson、David Langley、Francis Y. Lee、Punit Marathe、Arvind Mathur、Simone Oppenheimer、James Tarrant、John S. Tokarski、Gregory D. Vite、Dolatrai M. Vyas、Henry Wong、Tai W. Wong、Hongjian Zhang、Guifen Zhang

  DOI：10.1016/j.bmcl.2007.02.050

  日期：2007.5

  Novel C-5 aminomethyl pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.