N-[N-(9-fluorenylmethoxycarbonyl)-β-alanyl-L-leucyl-L-alanyl-L-leucyl]doxorubicin | 274913-06-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: N-[N-(9-fluorenylmethoxycarbonyl)-β-alanyl-L-leucyl-L-alanyl-L-leucyl]doxorubicin
• 英文别名: 9H-fluoren-9-ylmethyl N-[3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-oxopropyl]carbamate
• CAS: 274913-06-3
• 化学式: C₆₀H₇₁N₅O₁₇
• 分子量: 1134.25
• InChiKey: AYCAAKKNIVVSEE-YNKZOLHXSA-N

物化性质

• 沸点：
  1322.8±65.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  82
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  335
• 氢给体数：
  10
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N-[N-(9-fluorenylmethoxycarbonyl)-β-alanyl-L-leucyl-L-alanyl-L-leucyl]doxorubicin 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 N-(succinyl-β-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin
  参考文献：
  名称：

  N-Succinyl-(β-alanyl-l-leucyl-l-alanyl-l-leucyl)doxorubicin:  An Extracellularly Tumor-Activated Prodrug Devoid of Intravenous Acute Toxicity

  摘要：

  Intravenous administration of N-(beta -alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped versions of 4 such as the succinyl derivative 5 can be administered by the iv route at more than 10 times the LD50 of doxorubicin without inducing the acute toxic reaction, and they are active in vivo.

  DOI：

  10.1021/jm0108754
• 作为产物：
  描述：

  盐酸多柔比星 、 N-(9-fluorenylmethoxycarbonyl)-β-alanyl-L-leucyl-L-alanyl-L-leucine 在 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， 反应 2.0h， 以90%的产率得到N-[N-(9-fluorenylmethoxycarbonyl)-β-alanyl-L-leucyl-L-alanyl-L-leucyl]doxorubicin
  参考文献：
  名称：

  N-Succinyl-(β-alanyl-l-leucyl-l-alanyl-l-leucyl)doxorubicin:  An Extracellularly Tumor-Activated Prodrug Devoid of Intravenous Acute Toxicity

  摘要：

  Intravenous administration of N-(beta -alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped versions of 4 such as the succinyl derivative 5 can be administered by the iv route at more than 10 times the LD50 of doxorubicin without inducing the acute toxic reaction, and they are active in vivo.

  DOI：

  10.1021/jm0108754