N-(tert-butoxycarbonyl)-N-(4-aminobutyl)mesitylenesulfonamide | 161452-09-1

• 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: N-(tert-butoxycarbonyl)-N-(4-aminobutyl)mesitylenesulfonamide
• 英文别名: tert-butyl N-(4-aminobutyl)-N-(2,4,6-trimethylphenyl)sulfonylcarbamate
• CAS: 161452-09-1
• 化学式: C₁₈H₃₀N₂O₄S
• 分子量: 370.513
• InChiKey: LBPBZWDQBJENKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  98.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-N-(4-aminobutyl)mesitylenesulfonamide 在 sodium hydroxide 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 24.75h， 生成 1-(tert-butoxycarbonyl)-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
• 作为产物：
  描述：

  2,4,6-二甲基苯磺酰胺 在 镍 ammonium hydroxide 、 氢气 、 sodium hydride 、 sodium iodide 作用下， 以 甲醇 为溶剂， 25.0~170.0 ℃ 、7.33 kPa 条件下， 反应 39.42h， 生成 N-(tert-butoxycarbonyl)-N-(4-aminobutyl)mesitylenesulfonamide
  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。
• 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.