bis[(E)-5,6-(E)-15,16-cyclopropyl]-3,8,13,18-tetraazaeicosane

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: bis[(E)-5,6-(E)-15,16-cyclopropyl]-3,8,13,18-tetraazaeicosane
• 英文别名: N,N'-bis[[2-(ethylaminomethyl)cyclopropyl]methyl]butane-1,4-diamine
• 化学式: C₁₈H₃₈N₄
• 分子量: 310.527
• InChiKey: KHXVWBSQJUHBHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  15
• 环数：
  2.0
• 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：

  N-ethyl-N-[[2-[[4-[[2-[[ethyl-(2,4,6-trimethylphenyl)sulfonylamino]methyl]cyclopropyl]methyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl-(2,4,6-trimethylphenyl)sulfonylamino]methyl]cyclopropyl]methyl]-2,4,6-trimethylbenzenesulfonamide 在 氢溴酸 、 溶剂黄146 、 苯酚 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 bis[(E)-5,6-(E)-15,16-cyclopropyl]-3,8,13,18-tetraazaeicosane
  参考文献：
  名称：

  Cyclopropane-Containing Polyamine Analogues Are Efficient Growth Inhibitors of a Human Prostate Tumor Xenograft in Nude Mice

  摘要：

  Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell lines, while 7, 10, and 18 were efficacious against DU-145 and DuPro. Maximum tolerated doses (MTD) for all five compounds in a NCr-nu mouse model were determined at dosing schedules of q1d x 5 (ip) in two cycles with a break of 10 days between cycles. Their antitumor efficacies were then tested against DU-145 tumor xenografts in mice treated with all five agents at their respective MTDs. In addition, the efficacies of 7 and 10 against the same tumor xenograft were assessed at doses below their respective MTDs. In all experiments, administration began two weeks after tumor implantation. All compounds efficiently inhibited tumor growth for up to 50 days postimplantation, with negligible animal body weight loss. Tetramine 10 and hexamine 18 were the most efficient among the five analogues in arresting tumor growth. Tetramine 10 containing two cyclopropane rings had the lowest systemic toxicity as reflected in animal body weight loss. It was further assessed at a weekly administration regimen of (q1w x 4) in two cycles with a four-week break between the cycles. At this dosing schedule, 10 again efficiently arrested tumor growth with negligible effect on animal body weight. Tetramine 10 also arrested the growth of large tumors (ca. 2000 mm(3)) treated 66 days postimplantation. Studies on the metabolism of 10 showed that it accumulates in tumor within 6 h after the end of administration and reached a maximum level 72 h after cessation of dosing. Intracellular concentrations of 10 in liver and kidney were much smaller when compared to those in the tumor when measured 72 h after cessation of dosing. In liver and kidney, the deethyl metabolites of 10 accumulated over a 96 h period after cessation of dosing.

  DOI：

  10.1021/jm030175u

文献信息

• Cycloalkyl substituted polyamines for cancer therapy and methods of synthesis therefor
  申请人：Frydman Benjamin

  公开号：US20070287754A1

  公开（公告）日：2007-12-13

  Conformationally restricted polyamine compounds useful in treatment of cancer and other diseases marked by abnormal cell proliferation are disclosed. Improved methods of synthesizing such compounds are also disclosed. In one method of the invention, a carbene-bearing or carbene equivalent-bearing compound is reacted with the double bond of an alkene compound to form a cyclopropyl ring as the first step in the synthesis.

  本发明揭示了在治疗癌症和其他由异常细胞增殖引起的疾病中有用的构象限制的多胺化合物。本发明还揭示了改进的合成这种化合物的方法。在本发明的一种方法中，通过使含有卡宾或卡宾等效物的化合物与烯烃化合物的双键反应，形成环丙基环作为合成的第一步。
• US7453011B2
  申请人：——

  公开号：US7453011B2

  公开（公告）日：2008-11-18