[(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] 2-aminoacetate | 1016194-69-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 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] 2-aminoacetate
• CAS: 1016194-69-6
• 化学式: C₂₁H₂₂FN₅O₄
• 分子量: 427.435
• InChiKey: SJDOZKJTMVUAKV-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [(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] 2-(phenylmethoxycarbonylamino)acetate 在 palladium on activated charcoal ammonium formate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以84%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] 2-aminoacetate
  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

• [EN] PROCESS FOR THE PREPARATION OF [(1R), 2S]-2-AMINOPROPIONIC ACID 2-[4-(4-FLUORO-2-METHYL-1H-INDOL-5-YLOXY)-5-METHYLPYRROLO[2,1-f][1,2,4]TRIAZIN-6-YLOXY]-1-METHYLETHYL ESTER<br/>[FR] PROCÉDÉ DE SYNTHÈSE DU [(1R),2S]-2-AMINOPROPIONATE DE 2-[4-(4-FLUORO-2-MÉTHYL-1H-INDOL-5-YLOXY)-5-MÉTHYLPYRROLO[2,1-F][1,2,4]TRIAZIN-6-YLOXY]-1-MÉTHYLÉTHYLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2007124332A1

  公开（公告）日：2007-11-01

  [EN] The invention relates to an improved process for preparing [(1R), 2S]-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester of the formula: (I). Compound (I) has been shown to be useful for the treatment of certain types of cancer.
  [FR] La présente invention concerne un procédé amélioré de synthèse du [(1R),2S]-2-aminopropionate de 2-[4-(4-fluoro-2-méthyl-1H-indol-5-yloxy)-5-méthylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-méthyléthyle de formule : (I). Il a été démontré que le composé (I) pouvait être employé dans le traitement de certains types de cancers.