1-(12-amino-4,9-diazadodecyl)-2-methyl-3-(phenylmethoxy)-4(1H)-pyridinone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-(phenylmethoxy)-4(1H)-pyridinone
• 英文别名: 1-[3-[4-(3-Aminopropylamino)butylamino]propyl]-2-methyl-3-phenylmethoxypyridin-4-one
• 化学式: C₂₃H₃₆N₄O₂
• 分子量: 400.564
• InChiKey: AGALWDNMAZCYQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  79.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(苄氧基)-2-甲基-4H-吡喃-4-酮 、 spermine tetrahydrochloride 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-(phenylmethoxy)-4(1H)-pyridinone
  参考文献：
  名称：

  Polyamine−Iron Chelator Conjugate

  摘要：

  The current study demonstrates unequivocally that polyamines can serve as vectors for the intracellular delivery of the bidentate chelator 1,2-dimethyl-3-hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone conjugate 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-hydroxy4(1H)-pyridinone is assembled from spermine and 3-O-benzylmaltol. The conjugate is shown to form a 3:1 complex with Fe(III) and to be taken up by the polyamine transporter 1900-fold against a concentration gradient. The K-i of the conjugate is 3.7 muM vs spermidine for the polyamine transporter. The conjugate is also at least 230 times more active in suppressing the growth of L1210 murine leukemia cells than is the parent ligand, decreases the activities of the polyamine biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase, and upregulates spermidine-spermine N-1-acetyltransferase. However, the effect on native polyamine pools is a moderate one. These findings are in keeping with the idea that polyamines can also serve as efficient vectors for the intracellular delivery of other iron chelators.

  DOI：

  10.1021/jm0302694

文献信息

• Polyamine−Iron Chelator Conjugate
  作者：Raymond J. Bergeron、James S. McManis、April M. Franklin、Hua Yao、William R. Weimar

  DOI：10.1021/jm0302694

  日期：2003.12.1

  The current study demonstrates unequivocally that polyamines can serve as vectors for the intracellular delivery of the bidentate chelator 1,2-dimethyl-3-hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone conjugate 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-hydroxy4(1H)-pyridinone is assembled from spermine and 3-O-benzylmaltol. The conjugate is shown to form a 3:1 complex with Fe(III) and to be taken up by the polyamine transporter 1900-fold against a concentration gradient. The K-i of the conjugate is 3.7 muM vs spermidine for the polyamine transporter. The conjugate is also at least 230 times more active in suppressing the growth of L1210 murine leukemia cells than is the parent ligand, decreases the activities of the polyamine biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase, and upregulates spermidine-spermine N-1-acetyltransferase. However, the effect on native polyamine pools is a moderate one. These findings are in keeping with the idea that polyamines can also serve as efficient vectors for the intracellular delivery of other iron chelators.