EMC-Glu-Phe-Lys(Mtt)-PABC-doxorubicin | 1136860-49-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: EMC-Glu-Phe-Lys(Mtt)-PABC-doxorubicin
• CAS: 1136860-49-5
• 化学式: C₈₅H₉₁N₇O₂₁
• 分子量: 1546.69
• InChiKey: VQCAVVKGYAYVTJ-USFNXBBSSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.02
• 重原子数：
  113.0
• 可旋转键数：
  35.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  421.49
• 氢给体数：
  12.0
• 氢受体数：
  21.0

反应信息

• 作为反应物：
  描述：

  Phe-Lys(Mtt)-PABC 、 EMC-Glu-Phe-Lys(Mtt)-PABC-doxorubicin 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以70%的产率得到
  参考文献：
  名称：

  Development of dual-acting prodrugs for circumventing multidrug resistance

  摘要：

  We have developed a novel dual-acting maleimide-bearing prodrug that incorporates the anticancer agent doxorubicin and an inhibitor of the P-glycoprotein efflux pump that is over-expressed in multidrug resistant tumor cells. Additionally, the prodrug contains a 1,6-self-immolative spacer coupled to the dipeptide Phe-Lys that acts as a substrate for cathepsin B. The prodrug, once bound through its maleimide moiety to the cysteine-34 group of human serum albumin, was cleaved by cathepsin B and in tumor homogenates demonstrating a release of the anticancer agent doxorubicin and the inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.063
• 作为产物：
  描述：

  (S)-4-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-5-(((S)-1-(((S)-6-((diphenyl(p-tolyl)methyl)amino)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxohexan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-5-oxopentanoic acid 、 盐酸多柔比星 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以75%的产率得到EMC-Glu-Phe-Lys(Mtt)-PABC-doxorubicin
  参考文献：
  名称：

  Development of dual-acting prodrugs for circumventing multidrug resistance

  摘要：

  We have developed a novel dual-acting maleimide-bearing prodrug that incorporates the anticancer agent doxorubicin and an inhibitor of the P-glycoprotein efflux pump that is over-expressed in multidrug resistant tumor cells. Additionally, the prodrug contains a 1,6-self-immolative spacer coupled to the dipeptide Phe-Lys that acts as a substrate for cathepsin B. The prodrug, once bound through its maleimide moiety to the cysteine-34 group of human serum albumin, was cleaved by cathepsin B and in tumor homogenates demonstrating a release of the anticancer agent doxorubicin and the inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.063