1,6,11-tris(mesitylenesulfonyl)-1,6,11-triazatridecane | 161452-20-6

• 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: 1,6,11-tris(mesitylenesulfonyl)-1,6,11-triazatridecane
• 英文别名: N-[4-[4-[ethyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl]-2,4,6-trimethylbenzenesulfonamide
• CAS: 161452-20-6
• 化学式: C₃₇H₅₅N₃O₆S₃
• 分子量: 734.058
• InChiKey: CLZDUGOAZPZEIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  49
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  146
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1,6,11-tris(mesitylenesulfonyl)-1,6,11-triazatridecane 在 platinum(IV) oxide sodium hydroxide 、 氢气 、 sodium hydride 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 22.0 ℃ 、310.26 kPa 条件下， 反应 60.0h， 生成 3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaheneicosanecyanide
  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
• 作为产物：
  描述：

  2,4,6-二甲基苯磺酰胺 在 镍 ammonium hydroxide 、 sodium hydroxide 、 氢气 、 sodium hydride 、 三氟乙酸 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 170.0 ℃ 、7.33 kPa 条件下， 反应 65.0h， 生成 1,6,11-tris(mesitylenesulfonyl)-1,6,11-triazatridecane
  参考文献：
  名称：

  Antiproliferative Properties of Polyamine Analogs: A Structure-Activity Study

  摘要：

  A basis set of polyamine analogues was designed and synthesized. These compounds were used to initiate a systematic investigation of the role of chain length, terminal nitrogen alkyl group size, and symmetry of the methylene backbone in the antineoplastic properties of polyamine analogues. New synthetic methods predicated on our earlier polyamine fragment synthesis are described for accessing the tetraamines of interest. An unsymmetrically substituted diamine reagent, N-(tert-butoxycarbonyl)-N,N'-bis(mesitylene sulfonyl)-1,4- di-aminobutane, was developed for entry into unsymmetrical tetraamines. All of the tetraamines synthesized were first evaluated in a murine leukemia L1210 cell IC50 assay at 48 and 96 h. In an attempt to correlate this behavior with some aspect of polyamine metabolism, each compound was tested for its ability to compete with spermidine for the polyamine uptake apparatus, its impact on the polyamine biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), and its effect on the polyamine-catabolizing enzyme spermidine/spermine N-1-acetyltransferase (SSAT) and on polyamine pools. While there was no obvious correlation between the 48 and 96 h IC50'S and the impact of the analogues on polyamine metabolism, there were other structure-activity relationships. Correlations were observed to exist between chain length and IC50'S and between terminal alkyl substituents and impact on K-i, ODC, and AdoMetDC. Also, preliminary studies suggest a relationship may exist between the 48 and 96 h IC50's activities and the analogue's chronic toxicity in vivo. Finally, when the overall length of the polyamine backbone was held constant, the symmetry of the methylene chains of the polyamine fragments was shown to be unimportant to the compound's activity.

  DOI：

  10.1021/jm00047a004

文献信息

• Analogs of biologically active, naturally occurring polyamines, pharmaceutical compositions and methods of treatment
  申请人：University of Florida Research Foundation, Inc.

  公开号：US06342534B1

  公开（公告）日：2002-01-29

  Polyamines having the formula: or a salt thereof with a pharmaceutically acceptable acid wherein: R1-R6 may be the same or different and are alkyl, aryl, aryl alkyl, cycloalkyl, optionally having an alkyl chain interrupted by at least one etheric oxygen atom, or hydrogen; N1, N2, N3 and N4 are nitrogen atoms capable of protonation at physiological pH's; a and b may be the same or different and are integers from 1 to 4; A, B and C may be the same or different and are bridging groups which effectively maintain the distance between the nitrogen atoms such that the polyamines: (i) are capable of uptake by a target cell upon administration thereof to a human or non-human animal; and (ii) upon uptake by the target cell, competitively bind via an electrostatic interaction between the positively charged nitrogen atoms to substantially the same biological counter-anions as the intracellular natural polyamines in the target cell; the polyamines, upon binding to the biological counter-anion in the cell, function in a manner biologically different than the intracellular polyamines, the polyamines not occurring in nature; as well as pharmaceutical compositions embodying the polyamines and methods of treating patients requiring anti-neoplastic therapy.

  聚胺具有以下结构式：或其与药学上可接受的酸盐，其中：R1-R6可能相同也可能不同，是烷基、芳基、芳基烷基、环烷基，可以选择性地由至少一个醚氧原子中断的烷基链，或氢；N1、N2、N3和N4是在生理pH下能够质子化的氮原子；a和b可能相同也可能不同，是从1到4的整数；A、B和C可能相同也可能不同，是有效维持氮原子之间距离的桥接基团，使聚胺：(i)在向人类或非人类动物施用后能够被目标细胞吸收；(ii)在被目标细胞吸收后，通过正电荷氮原子之间的静电相互作用与目标细胞内的天然聚胺基本相同的生物对应阴离子竞争结合；聚胺，在细胞中与生物对应阴离子结合后，在生物学上与细胞内聚胺以不同方式发挥作用，这种聚胺在自然界中不存在；以及包含聚胺的药物组合物和治疗需要抗肿瘤治疗的患者的方法。
• 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
• Synthesis and growth regulatory activity of a prototype member of a new family of aminothiol radioprotectors
  作者：Richard R. Copp、Daniel D. Peebles、William E. Fahl

  DOI：10.1016/j.bmcl.2011.10.011

  日期：2011.10

  The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methylamino)-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. (C) 2011 Elsevier Ltd. All rights reserved.
• US7314959B2
  申请人：——

  公开号：US7314959B2

  公开（公告）日：2008-01-01