N¹-spermine 2-(1-adamantyl)acetamide

• 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: N¹-spermine 2-(1-adamantyl)acetamide
• 英文别名: 2-(1-adamantyl)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]acetamide
• 化学式: C₂₂H₄₂N₄O
• 分子量: 378.602
• InChiKey: NYLWLBLPPCSHRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  79.2
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-金刚烷乙酸 在 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 18.0h， 生成 N¹-spermine 2-(1-adamantyl)acetamide
  参考文献：
  名称：

  Amino Acid/Spermine Conjugates:  Polyamine Amides as Potent Spermidine Uptake Inhibitors

  摘要：

  In this paper we describe the synthesis and characterization of a series of simple spermine/amino acid conjugates, some of which potently inhibit the uptake of spermidine into MDAMB-231 breast cancer cells. The presence of an amide in the functionalized polyamine appeared to add to the affinity for the polyamine transporter. The extensive biological characterization of an especially potent analogue from this series, the Lys-Spm conjugate (31), showed this molecule will be an extremely useful tool for use in polyamine research. It was shown that the use of 31 in combination with DFMO led to a cytostatic growth inhibition of a variety of cancer cells, even when used in the presence of an extracellular source of transportable spermidine. It was furthermore shown that this combination effectively reduced the cellular levels of putrescine and spermidine while not affecting the levels of spermine. These facts together with the nontoxic nature of 31 make it a novel lead for further anticancer development.

  DOI：

  10.1021/jm0101040

文献信息

• Novel polyamine analogues as therapeutic and diagnostic agents
  申请人：ORIDIGM CORPORATION

  公开号：EP1085011A1

  公开（公告）日：2001-03-21

  Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating disease where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinatorial polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

  本发明揭示了具有比已知化合物低两个数量级的抑制常数的多胺转运抑制剂。这些多胺类似物是治疗需要抑制多胺转运或其他多胺结合蛋白的疾病的有用药物，例如癌症和血管成形术后的损伤。揭示了获得多胺类似物的新的化学合成方法，包括制备组合多胺库。这些方法产生的类似物具有理想的诊断和研究测定和治疗活性。本发明的测定方法对于高通量筛选与多胺系统相互作用的药物发现目标非常有用。
• US7208528B1
  申请人：——

  公开号：US7208528B1

  公开（公告）日：2007-04-24