N¹,N²⁰-didecanoyl-1,20-diamino-4,8,13,17-tetrazaicosane tetrakis(fluoroacetic acid)

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N¹,N²⁰-didecanoyl-1,20-diamino-4,8,13,17-tetrazaicosane tetrakis(fluoroacetic acid)
• 英文别名: N-[3-[3-[4-[3-[3-(decanoylamino)propylamino]propylamino]butylamino]propylamino]propyl]decanamide;2,2,2-trifluoroacetic acid
• 化学式: 4C₂HF₃O₂*C₃₆H₇₆N₆O₂
• 分子量: 1081.13
• InChiKey: ZXFZDHINKOVGPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.83
• 重原子数：
  51
• 可旋转键数：
  37
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  144
• 氢给体数：
  7
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  精胺 在 palladium dihydroxide ammonium hydroxide 、 氢气 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -78.0~25.0 ℃ 、344.74 kPa 条件下， 反应 69.0h， 生成 N¹,N²⁰-didecanoyl-1,20-diamino-4,8,13,17-tetrazaicosane tetrakis(fluoroacetic acid)
  参考文献：
  名称：

  Lipopolysaccharide Sequestrants:  Structural Correlates of Activity and Toxicity in Novel Acylhomospermines

  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 series of acylated homologated spermine compounds with LPS have been characterized. The optimal acyl chain length for effective sequestration of LPS was identified to be C-16 for the monoacyl compounds. The most promising of these compounds, 4e, binds LPS with an ED50 of 1.37 mu M. Nitric oxide production in murine J774A.1 cells, as well as TNF-alpha in human blood, is inhibited in a dose-dependent manner by 4e at concentrations orders of magnitude lower than toxic doses. Administration of 4e to D-galactosamine-sensitized mice challenged with supralethal doses of LPS provided significant protection against lethality. Potent antiendotoxic activity, low toxicity, and ease of synthesis render this class of compounds candidate endotoxin-sequestering agents of potential significant therapeutic value.

  DOI：

  10.1021/jm049449j

文献信息

• Lipopolysaccharide Sequestrants:  Structural Correlates of Activity and Toxicity in Novel Acylhomospermines
  作者：Kelly A. Miller、E. V. K. Suresh Kumar、Stewart J. Wood、Jens R. Cromer、Apurba Datta、Sunil A. David

  DOI：10.1021/jm049449j

  日期：2005.4.1

  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 series of acylated homologated spermine compounds with LPS have been characterized. The optimal acyl chain length for effective sequestration of LPS was identified to be C-16 for the monoacyl compounds. The most promising of these compounds, 4e, binds LPS with an ED50 of 1.37 mu M. Nitric oxide production in murine J774A.1 cells, as well as TNF-alpha in human blood, is inhibited in a dose-dependent manner by 4e at concentrations orders of magnitude lower than toxic doses. Administration of 4e to D-galactosamine-sensitized mice challenged with supralethal doses of LPS provided significant protection against lethality. Potent antiendotoxic activity, low toxicity, and ease of synthesis render this class of compounds candidate endotoxin-sequestering agents of potential significant therapeutic value.