N-(tert-butyl)-N-(4-bromobutyl)mesitylenesulfonamide | 161452-18-2

• 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-butyl)-N-(4-bromobutyl)mesitylenesulfonamide
• 英文别名: N-(4-bromobutyl)-N-(tert-butyl) mesitylenesulfonamide；N-(4-bromobutyl)-N-(tert-butyl)mesitylenesulfonamide；N-(4-bromobutyl)-N-tert-butyl-2,4,6-trimethylbenzenesulfonamide
• CAS: 161452-18-2
• 化学式: C₁₇H₂₈BrNO₂S
• 分子量: 390.385
• InChiKey: DMKKOTGTVMRUGS-UHFFFAOYSA-N

物化性质

• 沸点：
  464.265±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.235±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(tert-butyl)-N-(4-bromobutyl)mesitylenesulfonamide 在 氨 、 sodium 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 14.5h， 生成 N¹-(tert-butyl)-N¹⁴-ethylhomospermine
  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：

  2,4,6-三甲基苯磺酰氯 在 sodium hydroxide 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 24.28h， 生成 N-(tert-butyl)-N-(4-bromobutyl)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：——

  公开号：US20030100615A1

  公开（公告）日：2003-05-29

  Polyamines having the formula: 1 or a salt thereof with a pharmaceutically acceptable acid wherein: R 1 -R 6 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; N 1 , N 2 , N 3 and N 4 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.

  聚胺具有以下化学式：1或其与药用可接受酸盐，其中：R1-R6可能相同或不同，为烷基、芳基、芳基烷基、环烷基，或可由至少一个醚氧原子中断的烷基链组成，或氢；N1、N2、N3和N4是氮原子，在生理pH下能够质子化；a和b可能相同或不同，为1至4的整数；A、B和C可能相同或不同，是有效维持氮原子之间距离的桥联基团，使得聚胺：(i)能够在给予人类或非人类动物后被靶细胞吸收；以及(ii)在被靶细胞吸收后，通过正电荷氮原子之间的静电相互作用与靶细胞内的天然聚胺基本相同地与生物学反离子结合；这些聚胺在细胞内与生物反离子结合后，以生物学上与细胞内聚胺不同的方式发挥作用，这些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。
• Methods and compositions for the treatment of neurodegeneration
  申请人：University Of Florida Research Foundation, Inc.

  公开号：US05886051A1

  公开（公告）日：1999-03-23

  Methods and pharmaceutical compositions in unit dosage form for treating neurodegeneration in a human or non-human animal afflicted therewith wherein the active agent is a therapeutically effective amount of a polyamine having the formula: ##STR1## or a salt thereof with a pharmaceutically acceptable acid wherein: R.sub.1 and R.sub.6 may be the same or different and are hydrogen, alkyl, hydrocarbyl aryl, hydrocarbyl aryl alkyl, cycloalkyl, or any of the foregoing wherein the alkyl chain is interrupted by at least one etheric oxygen atom; N.sup.1, N.sup.2, N.sup.3 and N.sup.4 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 of variable length.

  用于治疗人类或非人类动物神经退行性疾病的单剂量形式的方法和药物组合物，其中活性药物是具有以下结构的聚胺的治疗有效量或其与药用酸的盐：R.sub.1和R.sub.6可以相同也可以不同，是氢、烷基、烃基芳基、烃基芳基烷基、环烷基或前述任何其中烷基链被至少一个醚氧原子打断的物质；N.sup.1、N.sup.2、N.sup.3和N.sup.4是在生理pH下能够质子化的氮原子；a和b可以相同也可以不同，是从1到4的整数；A、B和C可以相同也可以不同，是可变长度的桥联基。
• US5843959A
  申请人：——

  公开号：US5843959A

  公开（公告）日：1998-12-01
• US5886051A
  申请人：——

  公开号：US5886051A

  公开（公告）日：1999-03-23
• US6184232B1
  申请人：——

  公开号：US6184232B1

  公开（公告）日：2001-02-06