DP-343 | 113812-20-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: DP-343
• 英文别名: N¹,N¹²-dipropylspermine；N¹,N¹²-di-n-propylspermine；N,N'-bis[3-(propylamino)propyl]butane-1,4-diamine
• CAS: 113812-20-7
• 化学式: C₁₆H₃₈N₄
• 分子量: 286.505
• InChiKey: DEPAUFDLCOSVPH-UHFFFAOYSA-N

物化性质

• 沸点：
  395.6±10.0 °C(Predicted)
• 密度：
  0.873±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  48.1
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N¹,N⁴,N⁹,N¹²-tetrakis(mesityenesulfonyl)spermine 在 氢溴酸 、 sodium hydride 、 溶剂黄146 、 苯酚 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 DP-343
  参考文献：
  名称：

  多胺类似物止泻药：结构活性研究。

  摘要：

  描述了一组精胺多胺类似物的合成及其作为止泻药的评价。在啮齿动物蓖麻油诱发的腹泻模型中评估每种化合物降低粪便量和体重减轻的能力，这些剂量呈剂量依赖性。精胺药效基团被证明是构建止泻药的绝佳平台。化合物的活性非常取决于末端烷基的性质和分隔氮的亚甲基间隔基的几何形状。毒性特征还完全取决于这些相同的结构特征。根据皮下剂量反应数据和毒性概况，将两种化合物N（1），N（12）-二异丙精胺和N（1），N（12）-二乙基精胺进行了更全面的评估。这些测量包括正式的急性和慢性毒性试验，药物和代谢组织分布研究，以及这些类似物对组织多胺库的影响的评估。最后，N，N′-双[3-（乙基氨基）丙基]-反式1，4-环己二胺的显着活性强调需要进一步探索该构架作为构建其他止泻药的药效基团。

  DOI：

  10.1021/jm000277+

文献信息

• Synthetic polyamine analogs as antineoplastics
  作者：Raymond J. Bergeron、Allen H. Neims、James S. McManis、Thomas R. Hawthorne、John R. T. Vinson、Rita Bortell、Michael J. Ingeno

  DOI：10.1021/jm00401a019

  日期：1988.6

  In this paper, we report on the synthesis and biological activity of a number of N-alkylated spermine compounds. The dialkylspermines N1,N12-dimethylspermine (DMSPM-2), N1,N12-diethylspermine (DESPM-3), and N1,N12-dipropylspermine (DPSPM-4) are all shown to inhibit the growth of L1210 cells in culture with IC50 values of less than 1 microM at 96 h. Furthermore, DESPM-3 is shown to be similarly active against Daudi and HL-60 cells in culture. A structure-activity relationship is shown to exist between the position at which spermine is alkylated and its antiproliferative properties. The activity of 10 microM DESPM-3 against L1210 cells was shown to be cytostatic, with greater than 90% cell viability by trypan blue exclusion, even after a 144-h exposure. When L1210 cells were treated with 10 microM DESPM-3 over a 144-h period, their size and mitochondrial DNA content were gradually but substantially diminished. However, flow cytometric measurements of the nuclear DNA content of these treated cells at 96 h indicated only slightly reduced S and G2 populations and significant changes only after 144 h. A cloning assay performed on the cells after 96 h of exposure to this drug (10 microM) indicated that the cells were not growing. Finally, when male DBA/2 mice, inoculated with L1210 leukemia cells, were treated with DESPM-3, their life span was increased in excess of 200% relative to untreated controls. Moreover, many long-term survivors were apparently tumor free at the end of the experiment (60 days).
• Polyamine Analogue Antidiarrheals:  A Structure−Activity Study
  作者：Raymond J. Bergeron、Jan Wiegand、James S. McManis、William R. Weimar、Richard E. Smith、Samuel E. Algee、Tammy L. Fannin、Michael A. Slusher、Patti S. Snyder

  DOI：10.1021/jm000277+

  日期：2001.1.1

  spermine polyamine analogues and their evaluation as antidiarrheals are described. Each compound was assessed in a rodent castor oil-induced diarrhea model for its ability to reduce stool output and weight loss in a dose-dependent manner. The spermine pharmacophore is shown to be an excellent platform from which to construct antidiarrheals. The activity of the compounds is very dependent on both the nature

  描述了一组精胺多胺类似物的合成及其作为止泻药的评价。在啮齿动物蓖麻油诱发的腹泻模型中评估每种化合物降低粪便量和体重减轻的能力，这些剂量呈剂量依赖性。精胺药效基团被证明是构建止泻药的绝佳平台。化合物的活性非常取决于末端烷基的性质和分隔氮的亚甲基间隔基的几何形状。毒性特征还完全取决于这些相同的结构特征。根据皮下剂量反应数据和毒性概况，将两种化合物N（1），N（12）-二异丙精胺和N（1），N（12）-二乙基精胺进行了更全面的评估。这些测量包括正式的急性和慢性毒性试验，药物和代谢组织分布研究，以及这些类似物对组织多胺库的影响的评估。最后，N，N′-双[3-（乙基氨基）丙基]-反式1，4-环己二胺的显着活性强调需要进一步探索该构架作为构建其他止泻药的药效基团。