N-(3-((3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)phenyl)-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide | 887398-72-3

• 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-(3-((3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)phenyl)-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide
• 英文别名: 3-(4-methylpiperazin-1-yl)-N-[3-[[2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-6-yl]amino]phenyl]-5-(trifluoromethyl)benzamide
• CAS: 887398-72-3
• 化学式: C₃₂H₂₉F₃N₆O₂
• 分子量: 586.616
• InChiKey: JECVRFZSSMBKTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  43
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  92.5
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-硝基-4-溴苯乙酸 在 哌啶 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 palladium diacetate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 乙醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(3-((3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)phenyl)-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models

  摘要：

  Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications.

  DOI：

  10.1021/ml200261d

文献信息

• Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models
  作者：Pam Albaugh、Yi Fan、Yuan Mi、Fangxian Sun、Francisco Adrian、Nanxin Li、Yong Jia、Yelena Sarkisova、Andreas Kreusch、Tami Hood、Min Lu、Guoxun Liu、Shenlin Huang、Zuosheng Liu、Jon Loren、Tove Tuntland、Donald S. Karanewsky、H. Martin Seidel、Valentina Molteni

  DOI：10.1021/ml200261d

  日期：2012.2.9

  Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications.