2-(4-{3-methoxy-4-[7-(3-methoxypyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]phenyl}piperidin-1-yl)acetamide trifluoroacetic acid | 1353898-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(4-{3-methoxy-4-[7-(3-methoxypyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]phenyl}piperidin-1-yl)acetamide trifluoroacetic acid
• 英文别名: 2-[4-[3-Methoxy-4-[[7-(3-methoxypyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]acetamide;2,2,2-trifluoroacetic acid
• CAS: 1353898-64-2
• 化学式: C₂HF₃O₂*C₂₆H₂₉N₇O₃
• 分子量: 601.585
• InChiKey: BBLDIPLKSBTKKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.85
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(3-methoxy-4-nitrophenyl)-3,6-dihydropyridine-1(2H)-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~75.0 ℃ 、344.75 kPa 条件下， 反应 4.5h， 生成 2-(4-{3-methoxy-4-[7-(3-methoxypyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]phenyl}piperidin-1-yl)acetamide trifluoroacetic acid
  参考文献：
  名称：

  Strategies to Mitigate the Bioactivation of 2-Anilino-7-Aryl-Pyrrolo[2,1-f][1,2,4]triazines: Identification of Orally Bioavailable, Efficacious ALK Inhibitors

  摘要：

  Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel 2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described along with synthesis and biological activity. Piperidine-derived analogues showing minimal microsomal reactive metabolite formation were discovered. Potent, selective, and metabolically stable ALK inhibitors from this class were identified, and an orally bioavailable compound (32) with antitumor efficacy in ALK-driven xenografts in mouse models was extensively characterized.

  DOI：

  10.1021/jm2010767

文献信息

• Strategies to Mitigate the Bioactivation of 2-Anilino-7-Aryl-Pyrrolo[2,1-<i>f</i>][1,2,4]triazines: Identification of Orally Bioavailable, Efficacious ALK Inhibitors
  作者：Eugen F. Mesaros、Tho V. Thieu、Gregory J. Wells、Craig A. Zificsak、Jason C. Wagner、Henry J. Breslin、Rabindranath Tripathy、James L. Diebold、Robert J. McHugh、Ashley T. Wohler、Matthew R. Quail、Weihua Wan、Lihui Lu、Zeqi Huang、Mark S. Albom、Thelma S. Angeles、Kevin J. Wells-Knecht、Lisa D. Aimone、Mangeng Cheng、Mark A. Ator、Gregory R. Ott、Bruce D. Dorsey

  DOI：10.1021/jm2010767

  日期：2012.1.12

  Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel 2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described along with synthesis and biological activity. Piperidine-derived analogues showing minimal microsomal reactive metabolite formation were discovered. Potent, selective, and metabolically stable ALK inhibitors from this class were identified, and an orally bioavailable compound (32) with antitumor efficacy in ALK-driven xenografts in mouse models was extensively characterized.