N¹,N⁴,N⁸,N¹¹-tetrakis(mesitylenesulfonyl)norspermine | 161452-23-9

• 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,N⁸,N¹¹-tetrakis(mesitylenesulfonyl)norspermine
• 英文别名: 2,4,6-trimethyl-N-[3-[(2,4,6-trimethylphenyl)sulfonyl-[3-[(2,4,6-trimethylphenyl)sulfonyl-[3-[(2,4,6-trimethylphenyl)sulfonylamino]propyl]amino]propyl]amino]propyl]benzenesulfonamide
• CAS: 161452-23-9
• 化学式: C₄₅H₆₄N₄O₈S₄
• 分子量: 917.289
• InChiKey: IGEKBRSLPPOLJG-UHFFFAOYSA-N

物化性质

• 沸点：
  977.8±75.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  61
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  201
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N¹,N⁴,N⁸,N¹¹-tetrakis(mesitylenesulfonyl)norspermine 以92的产率得到N¹,N⁴,N⁸,N¹¹-tetrakis(mesitylenesulfonyl)-N¹,N¹¹-diethylnorspermine
  参考文献：
  名称：

  J. Med. Chem. 1994, 37, 3464-3476

  摘要：

  DOI：
• 作为产物：
  描述：

  N,N'-双(3-氨丙基)-1,3-丙二胺 以80的产率得到N¹,N⁴,N⁸,N¹¹-tetrakis(mesitylenesulfonyl)norspermine
  参考文献：
  名称：

  J. Med. Chem. 1994, 37, 3464-3476

  摘要：

  DOI：

文献信息

• A Comparison of Structure−Activity Relationships between Spermidine and Spermine Analogue Antineoplastics
  作者：Raymond J. Bergeron、Yang Feng、William R. Weimar、James S. McManis、Hristina Dimova、Carl Porter、Brian Raisler、Otto Phanstiel

  DOI：10.1021/jm960849j

  日期：1997.5.1

  A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N-1-acetyltransferase, the maintenance of cellular charge, i.e., cationic equivalence associated with the polyamines and their analogues, and compares their ability to compete with spermidine for transport. The findings clearly demonstrate that the activity of-the linear polyamine analogues is highly dependent on the length of the triamines and the size of the N-alpha,N-omega-substituents. It appears that there is an optimum chain length for various activities and that the larger the N-alpha,N-omega-alkyls, the less active the compound. Metabolic transformation including N-dealkylation of these compounds is also evaluated. While there is no monotonic relationship between chain length and the ability of the analogue to be metabolized, the dipropyl triamines are clearly more actively catabolized than the corresponding methyl and ethyl systems. A comparison of the triamines with the corresponding tetraamines is made throughout the text regarding both in vitro activity against L1210 cells and in vivo toxicity measurements, suggesting that several triamine analogues may offer therapeutic advantages over the corresponding tetraamines.
• Alkyl-Substituted Polyaminohydroxamic Acids:  A Novel Class of Targeted Histone Deacetylase Inhibitors
  作者：Sheeba Varghese、Deepak Gupta、Tiffany Baran、Anchalee Jiemjit、Steven D. Gore、Robert A. Casero,、Patrick M. Woster

  DOI：10.1021/jm0505009

  日期：2005.10.1

  The reversible acetylation of histones is critical for regulation of eukaryotic gene expression. The histone deacetylase inhibitors trichostatin (TSA, 1), MS-275 (2) and suberoylanilide, hydroxamic acid (SAHA, 3) arrest growth in transformed cells and in human tumor xenografts. However, 1-3 suffer from lack of specificity among the various HDAC isoforms, prompting us to design and synthesize polyaminohydroxamic acid (PAHA) derivatives 6-21. We felt that PAHAs would be selectively directed to chromatin and associated histones by the positively charged polyamine side chain. At 1 mu M, compounds 12, 15 and 20 inhibited HDAC by 74.86, 59.99 and 73.85%, respectively. Although 20 was a less potent HDAC inhibitor than 1, it was more potent than 2, more effective as an initiator of histone hyperacetylation, and significantly more effective than 2 at re-expressing p21(Waf1) in ML-1 leukemia cells. On the basis of these results, PAHAs 6-21 represent an important new chemical class of HDAC inhibitors.
• Antiproliferative Properties of Polyamine Analogs: A Structure-Activity Study
  作者：Raymond J. Bergeron、James S. McManis、Charles Z. Liu、Yang Feng、William R. Weimar、Gabriel R. Luchetta、Qianhong Wu、Jackqueline Ortiz-Ocasio、J. R. Timothy Vinson

  DOI：10.1021/jm00047a004

  日期：1994.10

  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.
• J. Med. Chem. 1994, 37, 3464-3476
  作者：

  DOI：——

  日期：——