N12-acetyl-N1,N3,N6-tris-(benzyloxycarbonyl)-1,12-diamino-3,6,9-triazadodecane | 1239137-81-5

• 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: N12-acetyl-N1,N3,N6-tris-(benzyloxycarbonyl)-1,12-diamino-3,6,9-triazadodecane
• 英文别名: benzyl N-[2-(3-acetamidopropylamino)ethyl]-N-[2-[phenylmethoxycarbonyl-[2-(phenylmethoxycarbonylamino)ethyl]amino]ethyl]carbamate
• CAS: 1239137-81-5
• 化学式: C₃₅H₄₅N₅O₇
• 分子量: 647.772
• InChiKey: PEKPZNYUNYUUDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  47
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N12-acetyl-N1,N3,N6-tris-(benzyloxycarbonyl)-1,12-diamino-3,6,9-triazadodecane 在 钯 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 N12-acetyl-1,12-diamino-3,6,9-triazadodecane
  参考文献：
  名称：

  Synthesis and Biological Characterization of Novel Charge-Deficient Spermine Analogues

  摘要：

  Biogenic polyamines, spermidine and spermine, are positively charged at physiological pH. They are present in all cells and essential for their growth and viability. Here we synthesized three novel derivatives of the isosteric charge-deficient spermine analogue 1,12-diamino-3,6,9-triazadodecane (SpmTrien, 5a) that are N(1)-Ac-SpmTrien (Sc), N(12)-Ac-SpmTrien (5b), and N(1),N(12)-diethyl-1,12-diamino-3,6,9-triazadodecane (N(1),N(12)-Et(2)-SpmTrien, 5d). 5a and 5d readily accumulated in DU145 cells at the same concentration range as natural polyamines and moderately competed for the uptake with putrescine (1) but not with spermine (4a) or spermidine (2). 5a efficiently down-regulated ornithine decarboxylase and decreased polyamine levels, while 5d proved to be inefficient, compared with N(1),N(11)-diethylnorspermine (6). None of the tested analogues were substrates for human recombinant spermine oxidase, but those having free aminoterminus, including 1,8-diamino-3,6-diazaoctane (Trien, 3a), were acetylated by mouse recombinant spermidine/spermine N(1)-acetyltransferase. 5a was acetylated to Sc and 5b, and the latter was further metabolized by acetylpolyamine oxidase to 3a, a drug used to treat Wilson's disease. Thus, 5a is a bioactive precursor of 3a with enhanced bioavailability.

  DOI：

  10.1021/jm100439p
• 作为产物：
  描述：

  N3,N6,N8-tris(benzyloxycarbonyl)-8-amino-3,6-diaza-1-octyl methanesulfonate 、 N-乙酰基-1,3-丙二胺 以 四氢呋喃 为溶剂， 反应 54.0h， 以0.97 g的产率得到N12-acetyl-N1,N3,N6-tris-(benzyloxycarbonyl)-1,12-diamino-3,6,9-triazadodecane
  参考文献：
  名称：

  Synthesis and Biological Characterization of Novel Charge-Deficient Spermine Analogues

  摘要：

  Biogenic polyamines, spermidine and spermine, are positively charged at physiological pH. They are present in all cells and essential for their growth and viability. Here we synthesized three novel derivatives of the isosteric charge-deficient spermine analogue 1,12-diamino-3,6,9-triazadodecane (SpmTrien, 5a) that are N(1)-Ac-SpmTrien (Sc), N(12)-Ac-SpmTrien (5b), and N(1),N(12)-diethyl-1,12-diamino-3,6,9-triazadodecane (N(1),N(12)-Et(2)-SpmTrien, 5d). 5a and 5d readily accumulated in DU145 cells at the same concentration range as natural polyamines and moderately competed for the uptake with putrescine (1) but not with spermine (4a) or spermidine (2). 5a efficiently down-regulated ornithine decarboxylase and decreased polyamine levels, while 5d proved to be inefficient, compared with N(1),N(11)-diethylnorspermine (6). None of the tested analogues were substrates for human recombinant spermine oxidase, but those having free aminoterminus, including 1,8-diamino-3,6-diazaoctane (Trien, 3a), were acetylated by mouse recombinant spermidine/spermine N(1)-acetyltransferase. 5a was acetylated to Sc and 5b, and the latter was further metabolized by acetylpolyamine oxidase to 3a, a drug used to treat Wilson's disease. Thus, 5a is a bioactive precursor of 3a with enhanced bioavailability.

  DOI：

  10.1021/jm100439p

文献信息

• Synthesis and Biological Characterization of Novel Charge-Deficient Spermine Analogues
  作者：Janne Weisell、Mervi T. Hyvönen、Merja R. Häkkinen、Nikolay A. Grigorenko、Marko Pietilä、Anita Lampinen、Sergey N. Kochetkov、Leena Alhonen、Jouko Vepsäläinen、Tuomo A. Keinänen、Alex R. Khomutov

  DOI：10.1021/jm100439p

  日期：2010.8.12

  Biogenic polyamines, spermidine and spermine, are positively charged at physiological pH. They are present in all cells and essential for their growth and viability. Here we synthesized three novel derivatives of the isosteric charge-deficient spermine analogue 1,12-diamino-3,6,9-triazadodecane (SpmTrien, 5a) that are N(1)-Ac-SpmTrien (Sc), N(12)-Ac-SpmTrien (5b), and N(1),N(12)-diethyl-1,12-diamino-3,6,9-triazadodecane (N(1),N(12)-Et(2)-SpmTrien, 5d). 5a and 5d readily accumulated in DU145 cells at the same concentration range as natural polyamines and moderately competed for the uptake with putrescine (1) but not with spermine (4a) or spermidine (2). 5a efficiently down-regulated ornithine decarboxylase and decreased polyamine levels, while 5d proved to be inefficient, compared with N(1),N(11)-diethylnorspermine (6). None of the tested analogues were substrates for human recombinant spermine oxidase, but those having free aminoterminus, including 1,8-diamino-3,6-diazaoctane (Trien, 3a), were acetylated by mouse recombinant spermidine/spermine N(1)-acetyltransferase. 5a was acetylated to Sc and 5b, and the latter was further metabolized by acetylpolyamine oxidase to 3a, a drug used to treat Wilson's disease. Thus, 5a is a bioactive precursor of 3a with enhanced bioavailability.