N-cyclopropyl-2,4-difluoro-5-[[6-(5-methylsulfonyl-1,3,4-oxadiazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide | 873091-39-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-cyclopropyl-2,4-difluoro-5-[[6-(5-methylsulfonyl-1,3,4-oxadiazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide
• CAS: 873091-39-5
• 化学式: C₂₂H₂₁F₂N₇O₄S
• 分子量: 517.516
• InChiKey: BJXYYROMLTUHDG-UHFFFAOYSA-N

物化性质

• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  DL-氨基丙醇 、 N-cyclopropyl-2,4-difluoro-5-[[6-(5-methylsulfonyl-1,3,4-oxadiazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 5-[[6-[5-(2-aminopropoxy)-1,3,4-oxadiazol-2-yl]-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-N-cyclopropyl-2,4-difluorobenzamide
  参考文献：
  名称：

  Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors

  摘要：

  Introduction of the 2,4-difluoro-5-(cyclopropylcarbamoyl) phenylamino group at the C-4 position of the pyrrolo[2,1-f] [ 1,2,4] triazine scaffold led to the discovery of a novel sub-series of inhibitors of VEGFR-2 kinase activity. Subsequent SAR studies on the 1,3,5-oxadiazole ring appended to the C-6 position of this new sub-family of pyrrolotriazines resulted in the identifiation of low nanomolar inhibitors of VEGFR-2. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.012
• 作为产物：
  描述：

  C₂₂H₂₁F₂N₇O₂S 在 间氯过氧苯甲酸 、 碳酸氢钠 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 6.0h， 以73%的产率得到N-cyclopropyl-2,4-difluoro-5-[[6-(5-methylsulfonyl-1,3,4-oxadiazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide
  参考文献：
  名称：

  Pyrrolotriazine kinase inhibitors

  摘要：

  本发明提供了式I的化合物及其药用可接受的盐。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，因此使它们可用作抗癌剂。式I的化合物还可用于治疗通过生长因子受体信号传导途径操作的其他疾病。

  公开号：

  US20060009454A1

文献信息

• Pyrrolotriazine kinase inhibitors
  申请人：Cai Zhen-wei

  公开号：US20060009454A1

  公开（公告）日：2006-01-12

  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的化合物及其药用可接受的盐。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，因此使它们可用作抗癌剂。式I的化合物还可用于治疗通过生长因子受体信号传导途径操作的其他疾病。
• Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors
  作者：Zhen-wei Cai、Donna Wei、Robert M. Borzilleri、Ligang Qian、Amrita Kamath、Steven Mortillo、Barri Wautlet、Benjamin J. Henley、Robert Jeyaseelan、John Tokarski、John T. Hunt、Rajeev S. Bhide、Joseph Fargnoli、Louis J. Lombardo

  DOI：10.1016/j.bmcl.2008.01.012

  日期：2008.2

  Introduction of the 2,4-difluoro-5-(cyclopropylcarbamoyl) phenylamino group at the C-4 position of the pyrrolo[2,1-f] [ 1,2,4] triazine scaffold led to the discovery of a novel sub-series of inhibitors of VEGFR-2 kinase activity. Subsequent SAR studies on the 1,3,5-oxadiazole ring appended to the C-6 position of this new sub-family of pyrrolotriazines resulted in the identifiation of low nanomolar inhibitors of VEGFR-2. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice. (c) 2008 Elsevier Ltd. All rights reserved.