N¹,N⁴-bis(mesitylenesulfonyl)-N⁴-ethyl-1,4-diaminobutane | 189341-51-3

• 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: N¹,N⁴-bis(mesitylenesulfonyl)-N⁴-ethyl-1,4-diaminobutane
• 英文别名: N-[4-[ethyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl]-2,4,6-trimethylbenzenesulfonamide
• CAS: 189341-51-3
• 化学式: C₂₄H₃₆N₂O₄S₂
• 分子量: 480.693
• InChiKey: JWQBKBNHDALVGJ-UHFFFAOYSA-N

物化性质

• 熔点：
  71.5-72 °C
• 沸点：
  627.7±65.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N¹,N⁴-bis(mesitylenesulfonyl)-N⁴-ethyl-1,4-diaminobutane 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 22.0h， 生成 SL-11118
  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：

  tert-butyl N-[4-[ethyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl]-N-(2,4,6-trimethylphenyl)sulfonylcarbamate 以100的产率得到N¹,N⁴-bis(mesitylenesulfonyl)-N⁴-ethyl-1,4-diaminobutane
  参考文献：
  名称：

  [EN] NOVEL POLYAMINE ANALOG CONJUGATES AND QUINONE CONJUGATES AS THERAPIES FOR CANCERS AND PROSTATE DISEASES
  [FR] NOUVEAUX CONJUGUES D'ANALOGUE DE POLYAMINE ET CONJUGUES DE QUINONE, UTILISES POUR LE TRAITEMENT DE CANCERS ET DE MALADIES DE LA PROSTATE

  摘要：

  提供一种肽共轭物，其中将细胞毒性和细胞增殖抑制剂，如多胺类似物或萘醌类化合物，与多肽共轭，该多肽可以被酶如前列腺特异性抗原（PSA）和半胱氨酸蛋白酶B识别和剪切，以及包含这些共轭物的组合物。还提供了使用这些共轭物治疗前列腺疾病的方法。

  公开号：

  WO2000066175A2

文献信息

• Cycloalkyl substituted polyamines for cancer therapy and methods of synthesis therefor
  申请人：SLIL Biomedical Corporation

  公开号：US20030195377A1

  公开（公告）日：2003-10-16

  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.

  抑制构象限制的多胺化合物可用于治疗癌症和其他以异常细胞增殖为特征的疾病。改进的合成这类化合物的方法也被揭示。在该发明的一种方法中，带有卡宾基或卡宾等效基团的化合物与烯烃化合物的双键发生反应，形成环丙基环作为合成的第一步。
• Synthesis and evaluation of unsymmetrical polyamine derivatives as antitumor agents
  作者：Jianhong Wang、Songqiang Xie、Yanjie Li、Yongjun Guo、Yuanfang Ma、Jin Zhao、Otto Phanstiel、Chaojie Wang

  DOI：10.1016/j.bmc.2008.05.035

  日期：2008.7

  counterpart 1. The ornithine decarboxylase and topoisomerase II inhibition experiments indicated that ODC and TOPO II were potential, but not unique targets of these conjugates. Furthermore, the in vivo antitumor activities illustrated that the representative conjugate 2f and the homospermidine analogue 1 evidently inhibited the tumor growth and significantly increased the survival time of mice-bearing

  制备了一系列不对称取代的多胺衍生物，并研究了它们在小鼠白血病L1210，黑色素瘤B16和HeLa细胞中的细胞毒性。体外细胞毒性表明，这些缀合物可以识别多胺转运蛋白，并且与未取代的对应物相比，即使引入末端烷基导致细胞毒性降低，N-乙基修饰的高精胺部分也可能作为高精胺成为另一种有效载体。鸟氨酸脱羧酶和拓扑异构酶II抑制实验表明ODC和TOPO II是潜在的，但不是这些结合物的唯一靶标。此外，
• SYNTHESIS AND GROWTH REGULATORY ACTIVITY OF A PROTOTYPE MEMBER OF A NEW FAMILY OF AMlNOTHIOL RADIOPROTECTORS
  申请人：Fahl William E.

  公开号：US20140107216A1

  公开（公告）日：2014-04-17

  The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol, and its polyamine and thiolated polyamine progenitors are reported. All of the molecules significantly inhibited growth of cultured normal human fibroblasts. The combination of an ROS-scavenging thiol group and a positively charged alkyl-amine backbone provided the most radioprotective aminothiol molecule.

  报道了PrC-210氨硫醇，3-(甲氨基)-2-((甲氨基)甲基)丙烷-1-硫醇及其多胺和硫化多胺前体的合成、生长抑制和放射防护活性。所有分子均显著抑制培养的正常人类成纤维细胞的生长。具有ROS清除硫基团和带正电的烷基胺骨架的组合提供了最具放射防护性的氨硫醇分子。
• <i>Cis-</i>Unsaturated Analogues of 3,8,13,18,23-Pentaazapentacosane (BE-4-4-4-4):  Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cell Lines
  作者：Venodhar K. Reddy、Aparajita Sarkar、Aldonia Valasinas、Laurence J. Marton、Hirak S. Basu、Benjamin Frydman

  DOI：10.1021/jm000310s

  日期：2001.2.1

  DU145, PC-3, and DuPro) using a MTT assay. LnCap and DU145 cells were very sensitive, PC-3 cells were relatively resistant, and DuPro cells were intermediate in sensitivity to most of these synthetic pentamines. In all cell lines, pentamines that had unsaturation(s) at the end of the chain showed the highest cell growth inhibitory effects. The cellular uptake, effects on cellular polyamine levels, and

  从我们以前对多胺-核酸相互作用的理化研究结果来看，我们得出的结论是，呈顺式构型的多胺类似物能够包裹双螺旋的主要凹槽，能够将天然多胺从其核酸结合位点移出，并具有抑制作用。细胞分裂。基于该假设，制备了九种不饱和五胺，其形式正式是由具有细胞毒性的五胺3,8,13,18,23-五aazapentacosane（BE-4-4-4-4）衍生而来，旨在提高抗肿瘤活性。将顺式双键引入到BE-4-4-4-4的饱和五氮杂五硼烷结构的所有可能位置中，以生成两个五碳杂酚，四个五碳二烯，两个五碳三烯和一个五碳四烯。顺式双键也应为混合功能氧化酶提供良好的靶标，该功能可以消除血清中不饱和五胺的积累，从而降低动物的全身毒性。我们使用MTT测定法确定了这些新的五胺在四种培养的人类前列腺癌细胞系（LnCap，DU145，PC-3和DuPro）中抑制生长的能力。LnCap和DU145细胞非常敏感，PC-3细胞具有相对抗性，而D
• OLIGOAMINE COMPOUNDS AND DERIVATIVES THEREOF FOR CANCER THERAPY
  申请人：Frydman Benjamin

  公开号：US20090124832A1

  公开（公告）日：2009-05-14

  Oligoamine compounds with anti-cancer and anti-proliferative activity are provided, as well as methods for making and using the compounds. The compounds are shown to be active against prostate cancer cell lines and against prostate cancer tumors in mice. The compounds are also useful in treatment of breast cancer and other cancers.

  提供具有抗癌和抗增殖活性的寡胺化合物，以及制备和使用这些化合物的方法。这些化合物已被证明对前列腺癌细胞系和小鼠前列腺癌肿瘤具有活性。这些化合物还可用于治疗乳腺癌和其他癌症。