6-(2-bromoethoxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine | 649735-76-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2-bromoethoxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine
• 英文别名: 6-(2-bromoethoxy)-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazine
• CAS: 649735-76-2
• 化学式: C₁₈H₁₆BrFN₄O₂
• 分子量: 419.253
• InChiKey: HWDVZKALBNHMNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(2-bromoethoxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine 、 (R)-3-吡咯烷醇 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以66 mg的产率得到(R)-1-(2-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)ethyl)pyrrolidin-3-ol
  参考文献：
  名称：

  Discovery and Preclinical Studies of (R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an In Vivo Active Potent VEGFR-2 Inhibitor

  摘要：

  A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo-[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a Substituted alkoxy group at the 6-position of the pyrrolo[2, 1-f][ 1,2,4]triazine core gave potent compounds. Biochemical potency, kinase selectivity, and pharmacokinetics of the series were optimized and in vitro safety liabilities were minimized to afford BMS-540215 (12). which demonstrated robust preclinical in vivo activity in human tumor xenograft models. The L-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors.

  DOI：

  10.1021/jm051106d
• 作为产物：
  描述：

  4-氟-5-羟基-2-甲基吲哚 在 palladium on activated charcoal 甲酸铵 、 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 6-(2-bromoethoxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine
  参考文献：
  名称：

  Discovery and Preclinical Studies of (R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an In Vivo Active Potent VEGFR-2 Inhibitor

  摘要：

  A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo-[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a Substituted alkoxy group at the 6-position of the pyrrolo[2, 1-f][ 1,2,4]triazine core gave potent compounds. Biochemical potency, kinase selectivity, and pharmacokinetics of the series were optimized and in vitro safety liabilities were minimized to afford BMS-540215 (12). which demonstrated robust preclinical in vivo activity in human tumor xenograft models. The L-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors.

  DOI：

  10.1021/jm051106d

文献信息

• Novel inhibitors of kinases
  申请人：——

  公开号：US20040072832A1

  公开（公告）日：2004-04-15

  The present invention provides compounds of formula I, 1 and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2 and FGFR-1, 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.

  本发明提供公式I的化合物及其药学上可接受的盐。公式I的化合物抑制生长因子受体的酪氨酸激酶活性，例如VEGFR-2和FGFR-1，因此使它们成为抗癌剂。公式I的化合物还可用于治疗与信号转导途径相关的其他疾病，这些途径通过生长因子受体运作。
• Inhibitors of kinases
  申请人：Bristol-Myers Squibb Company

  公开号：US07265113B2

  公开（公告）日：2007-09-04

  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 and FGFR-1, 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，以及其药学上可接受的盐。公式I的化合物抑制生长因子受体的酪氨酸激酶活性，如VEGFR-2和FGFR-1，因此使它们有用作抗癌剂。公式I的化合物也用于治疗与通过生长因子受体操作的信号转导途径相关的其他疾病。
• NOVEL INHIBITORS OF KINASES
  申请人：Bhide S. Rajeev

  公开号：US20070299075A1

  公开（公告）日：2007-12-27

  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 and FGFR-1, 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I式化合物及其药学上可接受的盐。I式化合物抑制生长因子受体如VEGFR-2和FGFR-1的酪氨酸激酶活性，因此可用作抗癌剂。I式化合物还可用于治疗通过生长因子受体操作的信号转导途径引起的其他疾病。
• Pyrrolo[2,1-f][1,2,4]triazine derivatives as kinase inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：EP2280012A2

  公开（公告）日：2011-02-02

  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 and FGFR-1, 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.

  本发明提供了式(I)化合物及其药学上可接受的盐类。式（I）化合物可抑制生长因子受体（如 VEGFR-2 和 FGFR-1）的酪氨酸激酶活性，因此可用作抗癌剂。式 (I) 化合物还可用于治疗与通过生长因子受体运行的信号转导通路有关的其他疾病。
• US6869952B2
  申请人：——

  公开号：US6869952B2

  公开（公告）日：2005-03-22