5-ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid | 310444-99-6

• 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: 5-ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid
• 英文别名: 4-(1-benzyl-1H-indazol-5-ylamino)-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid；4-[(1-benzylindazol-5-yl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid
• CAS: 310444-99-6
• 化学式: C₂₃H₂₀N₆O₂
• 分子量: 412.451
• InChiKey: WHYDOZDJTWFLEP-UHFFFAOYSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid 在 二苯基磷酸 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 {4-(1-benzyl-1H-indazol-5-ylamino)-5-ethylpyrrolo[2,1-f][1,2,4]triazin-6-yl}carbamic acid 2-(1H-imidazol-1-yl)ethyl ester
  参考文献：
  名称：

  New dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.

  DOI：

  10.1016/j.bmcl.2005.07.027
• 作为产物：
  描述：

  5-乙基-4-羟基吡咯并[1,2-f][1,2,4]三嗪-6-羧酸盐 在 lithium hydroxide 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 生成 5-ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid
  参考文献：
  名称：

  New dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.

  DOI：

  10.1016/j.bmcl.2005.07.027

文献信息

• Pyrrolotriazine inhibitors of kinases
  申请人：Bristol Myers Squibb Company

  公开号：US06982265B1

  公开（公告）日：2006-01-03

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, PDGFR, HER-1, HER-2, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了公式I的化合物及其药用可接受的盐。公式I的化合物抑制了诸如VEGFR-2、FGFR-1、PDGFR、HER-1、HER-2等生长因子受体的酪氨酸激酶活性，从而使其作为抗肿瘤剂具有用途。公式I的化合物也用于治疗通过生长因子受体运作的信号转导通路相关的其他疾病。
• C-6 modified indazolylpyrrolotriazines
  申请人：——

  公开号：US20040142931A1

  公开（公告）日：2004-07-22

  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.

  本发明提供了公式I1的化合物及其药学上可接受的盐。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。
• PYRROLOTRIAZINE INHIBITORS OF KINASES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1183033A1

  公开（公告）日：2002-03-06
• EP1183033A4
  申请人：——

  公开号：EP1183033A4

  公开（公告）日：2002-07-17
• EP1569937A4
  申请人：——

  公开号：EP1569937A4

  公开（公告）日：2007-08-08