[(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] 3-[(dimethylamino)methyl]benzoate | 1016195-11-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] 3-[(dimethylamino)methyl]benzoate
• CAS: 1016195-11-1
• 化学式: C₂₉H₃₀FN₅O₄
• 分子量: 531.587
• InChiKey: YABFYGFIFBKKDB-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  94
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  布立尼布 、 3-二甲基氨基甲基-苯甲酸 在 4-二甲氨基吡啶 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以56%的产率得到[(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] 3-[(dimethylamino)methyl]benzoate
  参考文献：
  名称：

  Discovery of Brivanib Alaninate ((S)-((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), A Novel Prodrug of Dual Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1 Kinase Inhibitor (BMS-540215)

  摘要：

  A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The L-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.

  DOI：

  10.1021/jm7013309

文献信息

• Discovery of Brivanib Alaninate ((<i>S</i>)-((<i>R</i>)-1-(4-(4-Fluoro-2-methyl-1<i>H</i>-indol-5-yloxy)-5-methylpyrrolo[2,1-<i>f</i>][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), A Novel Prodrug of Dual Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1 Kinase Inhibitor (BMS-540215)
  作者：Zhen-wei Cai、Yongzheng Zhang、Robert M. Borzilleri、Ligang Qian、Stephanie Barbosa、Donna Wei、Xiaoping Zheng、Lawrence Wu、Junying Fan、Zhongping Shi、Barri S. Wautlet、Steve Mortillo、Robert Jeyaseelan、Daniel W. Kukral、Amrita Kamath、Punit Marathe、Celia D’Arienzo、George Derbin、Joel C. Barrish、Jeffrey A. Robl、John T. Hunt、Louis J. Lombardo、Joseph Fargnoli、Rajeev S. Bhide

  DOI：10.1021/jm7013309

  日期：2008.3.1

  A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The L-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.