(Z,Z)-3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaeicosa-5,10-diene | 328260-29-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z,Z)-3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaeicosa-5,10-diene
• 英文别名: N-ethyl-N-[(Z)-4-[4-[[(Z)-4-[ethyl-(2,4,6-trimethylphenyl)sulfonylamino]but-2-enyl]-(2,4,6-trimethylphenyl)sulfonylamino]butyl-(2,4,6-trimethylphenyl)sulfonylamino]but-2-enyl]-2,4,6-trimethylbenzenesulfonamide
• CAS: 328260-29-3
• 化学式: C₅₂H₇₄N₄O₈S₄
• 分子量: 1011.45
• InChiKey: JOEWKEUIWOSYIB-CLFAGFIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  68
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  183
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (Z,Z)-3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaeicosa-5,10-diene 在 氢溴酸 、 溶剂黄146 、 苯酚 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 (Z,Z)-3,8,13,18-tetraazaeicosa-5,15-diene
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹⁴N-Bisethylhomospermine (BE-4-4-4):  Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cells

  摘要：

  Twelve analogues of N-1,N-14-bisethylhomospermine (BE-4-4-4) with restricted conformations were synthesized in the search for cancer chemotherapeutic agents with higher cytotoxic activities and lower systemic toxicities than BE-4-4-4. The central butane segment of BE-4-4-4 was replaced with a 1,2-substituted cyclopropane ring, a 1,2-substituted cyclobutane ring, and a 2-butene residue. In each case, the cis/trans-isomeric pair was synthesized. Cis-monounsaturation(s) was also introduced at the outer butane segment(s) of BE-4-4-4. The two possible cis-dienes and a cis-triene formally derived from the tetraazaeicosane skeleton of BE-4-4-4 were also prepared. Four cultured human prostate cancer cell lines (LnCap, DU145, DuPro, and PC-3) were treated with the new tetramines to examine their effects on cell growth with a MTT assay. One representative cell line (DuPro) was selected to further study the cellular uptake of the novel tetramines, their effects on intracellular polyamine pools, and their cytotoxicity. All tetramines entered the cells, reduced cellular putrescine and spermidine pools while exerting only a small effect on the spermine pool, inhibited cell growth, and killed 2-3 log; of cells after 6 days of treatment at 10 muM. Four new tetramines, the two cyclopropyl isomers, the trans-cyclobutyl isomer, and the (5Z)-tetraazaeicosene, were more cytotoxic than their saturated counterpart (BE-4-4-4). Their cytotoxicity, however, could not be correlated either with their cellular uptake or with their ability to deplete intracellular polyamine pools. We attribute their cytotoxicity to their specific molecular structures. The cytotoxicity was markedly reduced when the central butane segment was deprived of its rotational freedom by replacing it with a double bond. Introduction of a triple bond or a benzene-1,2-dimethyl residue at the central segment of the polyamine chain, led to complete loss of biological activity. The conformationally restricted alicyclic derivatives were not only more cytotoxic than was the freely rotating BE-4-4-4 by several orders of magnitude but also had much lower systemic toxicities than the latter. Thus, we obtained new tetramines with a wider therapeutic window than BE-4-4-4.

  DOI：

  10.1021/jm000309t
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 在 氢氧化钾 、 苄基三乙基溴化铵 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (Z,Z)-3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaeicosa-5,10-diene
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹⁴N-Bisethylhomospermine (BE-4-4-4):  Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cells

  摘要：

  Twelve analogues of N-1,N-14-bisethylhomospermine (BE-4-4-4) with restricted conformations were synthesized in the search for cancer chemotherapeutic agents with higher cytotoxic activities and lower systemic toxicities than BE-4-4-4. The central butane segment of BE-4-4-4 was replaced with a 1,2-substituted cyclopropane ring, a 1,2-substituted cyclobutane ring, and a 2-butene residue. In each case, the cis/trans-isomeric pair was synthesized. Cis-monounsaturation(s) was also introduced at the outer butane segment(s) of BE-4-4-4. The two possible cis-dienes and a cis-triene formally derived from the tetraazaeicosane skeleton of BE-4-4-4 were also prepared. Four cultured human prostate cancer cell lines (LnCap, DU145, DuPro, and PC-3) were treated with the new tetramines to examine their effects on cell growth with a MTT assay. One representative cell line (DuPro) was selected to further study the cellular uptake of the novel tetramines, their effects on intracellular polyamine pools, and their cytotoxicity. All tetramines entered the cells, reduced cellular putrescine and spermidine pools while exerting only a small effect on the spermine pool, inhibited cell growth, and killed 2-3 log; of cells after 6 days of treatment at 10 muM. Four new tetramines, the two cyclopropyl isomers, the trans-cyclobutyl isomer, and the (5Z)-tetraazaeicosene, were more cytotoxic than their saturated counterpart (BE-4-4-4). Their cytotoxicity, however, could not be correlated either with their cellular uptake or with their ability to deplete intracellular polyamine pools. We attribute their cytotoxicity to their specific molecular structures. The cytotoxicity was markedly reduced when the central butane segment was deprived of its rotational freedom by replacing it with a double bond. Introduction of a triple bond or a benzene-1,2-dimethyl residue at the central segment of the polyamine chain, led to complete loss of biological activity. The conformationally restricted alicyclic derivatives were not only more cytotoxic than was the freely rotating BE-4-4-4 by several orders of magnitude but also had much lower systemic toxicities than the latter. Thus, we obtained new tetramines with a wider therapeutic window than BE-4-4-4.

  DOI：

  10.1021/jm000309t