N¹-(4-carbomethoxy)benzoyl-N⁴,N⁹,N¹²-tris(tert-butoxycarbonyl)spermine | 857941-07-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N¹-(4-carbomethoxy)benzoyl-N⁴,N⁹,N¹²-tris(tert-butoxycarbonyl)spermine
• 英文别名: Methyl 4-[3-[(2-methylpropan-2-yl)oxycarbonyl-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]butyl]amino]propylcarbamoyl]benzoate
• CAS: 857941-07-2
• 化学式: C₃₄H₅₆N₄O₉
• 分子量: 664.84
• InChiKey: BYBUNDHMRFYGGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  47
• 可旋转键数：
  22
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N¹-(4-carbomethoxy)benzoyl-N⁴,N⁹,N¹²-tris(tert-butoxycarbonyl)spermine 在 sodium hydroxide 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 4-[3-[4-(3-Aminopropylamino)butylamino]propylcarbamoyl]benzoic acid
  参考文献：
  名称：

  Polyamine-Vectored Iron Chelators:  The Role of Charge

  摘要：

  The utility of polyamines as vectors for the intracellular transport of iron chelators is further described. Consistent with earlier results with polyamine analogues, these studies underscore the importance of charge in the design of polyamine-vectored chelators. Four polyamine conjugates are synthesized, two of tereplithalic acid [N-1-(4-carboxy)benzoylspermine (7) and its methyl ester (6)] and two of (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT] [(S)-4,5-dihydro-2-[2-hydroxy-4-(12-amino-5,9-diazadodecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid (10) and its ethyl ester (9)]. These four molecules were evaluated in murine leukemia L1210 cells for their impact on cell proliferation (48- and 96-h IC50 values), their ability to compete with spermidine for the polyamine transport apparatus (K-i), and their intracellular accumulation. The data revealed that when neutral molecules (cargo fragments) were fixed to the polyamine vector, the conjugates competed well with spermidine for transport and were accumulated intracellularly to millimolar levels. However, this was not the case when the cargo fragments were negatively charged. Metabolic studies of the polyamine-vectored (S)-4'-(HO)-DADFTs in rodents indicated that not only did the expected deaminopropylation step occur, but also a surprisingly high level of oxidative deamination at the terminal primary nitrogens took place. Finally, the iron-clearing efficiency of the (S)-4'-(HO)-DADFT conjugates was determined in a bile-duct-cannulated rodent model. Attaching the ligand to a polyamine vector had a profound effect on increasing the iron-clearing efficiency of this chelator relative to its parent drug.

  DOI：

  10.1021/jm048974f
• 作为产物：
  描述：

  对苯二甲酸单甲酯 、 2-甲基-2-丙基(3-氨基丙基)[4-({[(2-甲基-2-丙基)氧基]羰基}[3-({[(2-甲基-2-丙基)氧基]羰基}氨基)丙基]氨基)丁基]氨基甲酸酯 在 N,N'-羰基二咪唑 作用下， 生成 N¹-(4-carbomethoxy)benzoyl-N⁴,N⁹,N¹²-tris(tert-butoxycarbonyl)spermine
  参考文献：
  名称：

  [EN] POLYAMINE-METAL CHELATOR CONJUGATES
  [FR] CONJUGUES POLYAMINE-CHELATEUR DE METAL

  摘要：

  公开号：

  WO2005023310A3

文献信息

• [EN] POLYAMINE-METAL CHELATOR CONJUGATES<br/>[FR] CONJUGUES POLYAMINE-CHELATEUR DE METAL
  申请人：UNIV FLORIDA

  公开号：WO2005023310A3

  公开（公告）日：2005-04-21
• Polyamine-Vectored Iron Chelators:  The Role of Charge
  作者：Raymond J. Bergeron、Neelam Bharti、Jan Wiegand、James S. McManis、Hua Yao、Laszlo Prokai

  DOI：10.1021/jm048974f

  日期：2005.6.1

  The utility of polyamines as vectors for the intracellular transport of iron chelators is further described. Consistent with earlier results with polyamine analogues, these studies underscore the importance of charge in the design of polyamine-vectored chelators. Four polyamine conjugates are synthesized, two of tereplithalic acid [N-1-(4-carboxy)benzoylspermine (7) and its methyl ester (6)] and two of (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT] [(S)-4,5-dihydro-2-[2-hydroxy-4-(12-amino-5,9-diazadodecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid (10) and its ethyl ester (9)]. These four molecules were evaluated in murine leukemia L1210 cells for their impact on cell proliferation (48- and 96-h IC50 values), their ability to compete with spermidine for the polyamine transport apparatus (K-i), and their intracellular accumulation. The data revealed that when neutral molecules (cargo fragments) were fixed to the polyamine vector, the conjugates competed well with spermidine for transport and were accumulated intracellularly to millimolar levels. However, this was not the case when the cargo fragments were negatively charged. Metabolic studies of the polyamine-vectored (S)-4'-(HO)-DADFTs in rodents indicated that not only did the expected deaminopropylation step occur, but also a surprisingly high level of oxidative deamination at the terminal primary nitrogens took place. Finally, the iron-clearing efficiency of the (S)-4'-(HO)-DADFT conjugates was determined in a bile-duct-cannulated rodent model. Attaching the ligand to a polyamine vector had a profound effect on increasing the iron-clearing efficiency of this chelator relative to its parent drug.