Phosphoric acid dibenzyl ester 3-[(S)-4-(2,5-difluoro-phenyl)-1-((S)-2-hydroxy-3,3-dimethyl-butyryl)-2,5-dihydro-1H-pyrrol-2-yl]-phenyl ester | 884651-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: Phosphoric acid dibenzyl ester 3-[(S)-4-(2,5-difluoro-phenyl)-1-((S)-2-hydroxy-3,3-dimethyl-butyryl)-2,5-dihydro-1H-pyrrol-2-yl]-phenyl ester
• CAS: 884651-24-5
• 化学式: C₃₆H₃₆F₂NO₆P
• 分子量: 647.656
• InChiKey: NJJQVZFHAXQJNU-SZAHLOSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.26
• 重原子数：
  46.0
• 可旋转键数：
  11.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  85.3
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Phosphoric acid dibenzyl ester 3-[(S)-4-(2,5-difluoro-phenyl)-1-((S)-2-hydroxy-3,3-dimethyl-butyryl)-2,5-dihydro-1H-pyrrol-2-yl]-phenyl ester 在 palladium on activated charcoal 1,4-环己二烯 作用下， 以 甲醇 为溶剂， 以95%的产率得到3-{(2S)-4-(2,5-difluorophenyl)-1-[(2S)-2-hydroxy-3,3-dimethylbutanoyl]-2,5-dihydro-1H-pyrrol-2-yl}phenyl dihydrogen phosphate
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 3: Synthesis and evaluation of phenolic 2,4-diaryl-2,5-dihydropyrroles with reduced hERG binding and employment of a phosphate prodrug strategy for aqueous solubility

  摘要：

  2,4-Diaryl-2,5-dihydropyrroles have been discovered to be novel, potent and water-soluble inhibitors of KSP, an emerging therapeutic target for the treatment of cancer. A potential concern for these basic KSP inhibitors (1 and 2) was hERG binding that can be minimized by incorporation of a potency-enhancing C2 phenol combined with neutral N1 side chains. Aqueous solubility was restored to these, and other, non-basic inhibitors, through a phosphate prodrug strategy. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.094
• 作为产物：
  描述：

  在 四氯化碳 、 4-二甲氨基吡啶 、 二乙基异丙基胺 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 Phosphoric acid dibenzyl ester 3-[(S)-4-(2,5-difluoro-phenyl)-1-((S)-2-hydroxy-3,3-dimethyl-butyryl)-2,5-dihydro-1H-pyrrol-2-yl]-phenyl ester
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 3: Synthesis and evaluation of phenolic 2,4-diaryl-2,5-dihydropyrroles with reduced hERG binding and employment of a phosphate prodrug strategy for aqueous solubility

  摘要：

  2,4-Diaryl-2,5-dihydropyrroles have been discovered to be novel, potent and water-soluble inhibitors of KSP, an emerging therapeutic target for the treatment of cancer. A potential concern for these basic KSP inhibitors (1 and 2) was hERG binding that can be minimized by incorporation of a potency-enhancing C2 phenol combined with neutral N1 side chains. Aqueous solubility was restored to these, and other, non-basic inhibitors, through a phosphate prodrug strategy. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.094