L-Lys(3,3-dimethyl-1-butane)-N1-spermine | 862981-11-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: L-Lys(3,3-dimethyl-1-butane)-N1-spermine
• CAS: 862981-11-1
• 化学式: C₄₂H₈₂N₆O₉
• 分子量: 815.148
• InChiKey: SODNOPHFAYFXJH-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.75
• 重原子数：
  57.0
• 可旋转键数：
  22.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  176.87
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  L-Lys(3,3-dimethyl-1-butane)-N1-spermine 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以96%的产率得到N¹-[L-Lys(N^ε-3,3-dimethyl-1-butyl)]-spermine pentakis(hydrochloride)
  参考文献：
  名称：

  Lysine–spermine conjugates: hydrophobic polyamine amides as potent lipopolysaccharide sequestrants

  摘要：

  Lipopolysaccharides (LPS), otherwise termed `endotoxins' are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of `Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.038
• 作为产物：
  描述：

  Boc-L-Lys(Cbz)-N1-spermine-Boc3 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 三乙胺 、 原甲酸三甲酯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 L-Lys(3,3-dimethyl-1-butane)-N1-spermine
  参考文献：
  名称：

  Lysine–spermine conjugates: hydrophobic polyamine amides as potent lipopolysaccharide sequestrants

  摘要：

  Lipopolysaccharides (LPS), otherwise termed `endotoxins' are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of `Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.038

文献信息

• Hydrophobic polyamine amides as potent lipopolysaccharide sequestrants
  申请人：Burns R. Mark

  公开号：US20060122279A1

  公开（公告）日：2006-06-08

  Lysine-spermine conjugates with a long-chain aliphatic (C 12 -C 20 ) substituent at R 1 bind and neutralize bacterial lipopolysaccharides. These compounds reduce lethality in a murine model of lipopolysaccharide-induced shock, and may serve as novel leads for developing novel anti-lipopolysaccharide agents for the therapy of Gram-negative sepsis. These compounds are represented by the formula: wherein X is O or H, H; R is a hydrophobic C 12 -C 20 chain and Y is -NH 2 or -H; and pharmaceutically acceptable salts thereof and prodrugs thereof.

  赖氨酸-亚精胺共轭物与R1位点上的长链脂肪族（C12-C20）取代基结合并中和细菌脂多糖。这些化合物可以减少脂多糖诱导的休克小鼠模型中的致死率，并可作为开发治疗革兰氏阴性败血症的新型抗脂多糖药物的新颖先导化合物。这些化合物的化学式为：其中X为O或H，H；R为亲水性的C12-C20链，Y为-NH2或-H；以及其药学上可接受的盐和前药。