N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-β-D-glucurono-6,3-lactonide | 1256382-19-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-β-D-glucurono-6,3-lactonide
• 英文别名: N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-D-glucurono-6,3-lactonide
• CAS: 1256382-19-0
• 化学式: C₂₀H₂₈Cl₂N₂O₆
• 分子量: 463.358
• InChiKey: GCXJCQCBABOLRJ-RHQZKXFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.36
• 重原子数：
  30.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  102.7
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  D-glucurono-6,3-lactone 、 N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamine 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 (S,Z)-N-(4-(4-(bis(2-chloroethyl)amino)phenyl)butyl)-2-((2R,3R,4S)-3,4-dihydroxy-5-oxotetrahydrofuran-2-yl)-2-hydroxyethan-1-imine oxide 、 N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-β-D-glucurono-6,3-lactonide
  参考文献：
  名称：

  Assessment of Chemoselective Neoglycosylation Methods Using Chlorambucil as a Model

  摘要：

  To systematically assess the impact of glycosylation and the corresponding chemoselective linker upon the anticancer activity/selectivity of the drug chlorambucil, herein we report the synthesis and anticancer activities of a 63-member library of chlorambucil-based neoglycosides. A comparison of N-alkoxyamine-. N-acylhydrazine-, and N-hydroxyamine-based chemoselective glycosylation of chlorambucil revealed sugar- and linker-dependent partitioning among open- and closed-ring neoglycosides and corresponding sugar-dependent variant biological activity. Cumulatively, this study represents the First neoglycorandomization of a synthetic drug and expands our understanding of the impact of sugar structure upon product distribution/equilibria in the context of N-alkoxyamino-, N-hydroxyamino-, and N-acylhydrazine-based chemoselective glycosylation. This study also revealed several analogues with increased in vitro anticancer activity, most notably D-threoside 60 (NSC 748747), which displayed much broader tumor specificity and notably increased potency over the parent drug.

  DOI：

  10.1021/jm101024j