di-tert-butyl(((anthracene-9,10-diylbis(methylene))bis(azanediyl))bis(butane-4,1-diyl))bis((4-((tert-butoxycarbonyl)(methyl)amino)butyl)carbamate) | 1446751-82-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: di-tert-butyl(((anthracene-9,10-diylbis(methylene))bis(azanediyl))bis(butane-4,1-diyl))bis((4-((tert-butoxycarbonyl)(methyl)amino)butyl)carbamate)
• 英文别名: tert-butyl N-methyl-N-[4-[4-[[10-[[4-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butylamino]methyl]anthracen-9-yl]methylamino]butyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl]carbamate
• CAS: 1446751-82-1
• 化学式: C₅₄H₈₈N₆O₈
• 分子量: 949.328
• InChiKey: YCMTVYQHRJQGNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  68
• 可旋转键数：
  32
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  di-tert-butyl(((anthracene-9,10-diylbis(methylene))bis(azanediyl))bis(butane-4,1-diyl))bis((4-((tert-butoxycarbonyl)(methyl)amino)butyl)carbamate) 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.67h， 以93%的产率得到N¹,N¹′-[anthracene-9,10-diylbis(methylene)]bis{N⁴-[4-(methylamino)butyl]butane-1,4-diamine} hexahydrochloride
  参考文献：
  名称：

  Development of Polyamine Transport Ligands with Improved Metabolic Stability and Selectivity against Specific Human Cancers

  摘要：

  Polyamine homeostasis is critical for life and is accomplished via a balance of polyamine biosynthesis, degradation, and transport. Rapidly dividing cancer cells have been shown to have high polyamine transport activity compared to normal cells, likely due to their high requirement for polyamine metabolites. The polyamine transport system (PTS) is a therapeutically relevant target, as it can provide selective drug delivery to cancer cells. This report describes the synthesis and biological evaluation of multimeric polyamine derivatives as efficient PTS ligands. Arylmethyl-polyamine derivatives were synthesized to address two important concerns in PTS drug design: (a) PTS selectivity and (b) stability to amine oxidases. N-1,N-1'-[Naphthalene-1,4-diylbis(methylene)]bis{N-4-[4-(methylamino)butyl])-butane-1,4-diamine}, 3b, was found to have an optimal balance between these parameters and demonstrated excellent targeting of melanoma (e.g., MALME-3M) and breast cancer cells (e.g., T47D) over other cancer cell lines. These results provide a method to selectively target cancers via their intrinsic need for polyamine metabolites.

  DOI：

  10.1021/jm400496a
• 作为产物：
  描述：

  methanesulfonic acid 4-(tert-butoxycarbonyl-methyl-amino)-butyl ester 在 potassium carbonate 、 水杨醛 、 sodium sulfate 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.83h， 生成 di-tert-butyl(((anthracene-9,10-diylbis(methylene))bis(azanediyl))bis(butane-4,1-diyl))bis((4-((tert-butoxycarbonyl)(methyl)amino)butyl)carbamate)
  参考文献：
  名称：

  [EN] POLYAMINE TRANSPORT SELECTIVE THERAPEUTIC AGENTS WITH ENHANCED STABILITY
  [FR] AGENTS THÉRAPEUTIQUES SÉLECTIFS EN TERMES DE TRANSPORT DES POLYAMINES À STABILITÉ PLUS ÉLEVÉE

  摘要：

  本文披露了二取代芳基多胺化合物及其制备和使用方法。这些二取代多胺化合物作为PTS靶向剂，能够有选择性地靶向多胺转运系统（PTS），具有高效性，并且在胺氧化酶存在的情况下具有改善的稳定性。

  公开号：

  WO2013148230A1

文献信息

• [EN] POLYAMINE TRANSPORT SELECTIVE THERAPEUTIC AGENTS WITH ENHANCED STABILITY<br/>[FR] AGENTS THÉRAPEUTIQUES SÉLECTIFS EN TERMES DE TRANSPORT DES POLYAMINES À STABILITÉ PLUS ÉLEVÉE
  申请人：UNIV CENTRAL FLORIDA RES FOUND

  公开号：WO2013148230A1

  公开（公告）日：2013-10-03

  Disclosed herein are di-substituted aryl polyamine compounds and methods of making and using the same. The di-substituted polyamine compounds act as PTS targeting agents, which selectively target the polyamine transport system (PTS) with high efficacy and have improved stability in the presence of amine oxidases.

  本文披露了二取代芳基多胺化合物及其制备和使用方法。这些二取代多胺化合物作为PTS靶向剂，能够有选择性地靶向多胺转运系统（PTS），具有高效性，并且在胺氧化酶存在的情况下具有改善的稳定性。
• Development of Polyamine Transport Ligands with Improved Metabolic Stability and Selectivity against Specific Human Cancers
  作者：Aaron Muth、Joseph Kamel、Navneet Kaur、Allyson C. Shicora、Iraimoudi S. Ayene、Susan K. Gilmour、Otto Phanstiel

  DOI：10.1021/jm400496a

  日期：2013.7.25

  Polyamine homeostasis is critical for life and is accomplished via a balance of polyamine biosynthesis, degradation, and transport. Rapidly dividing cancer cells have been shown to have high polyamine transport activity compared to normal cells, likely due to their high requirement for polyamine metabolites. The polyamine transport system (PTS) is a therapeutically relevant target, as it can provide selective drug delivery to cancer cells. This report describes the synthesis and biological evaluation of multimeric polyamine derivatives as efficient PTS ligands. Arylmethyl-polyamine derivatives were synthesized to address two important concerns in PTS drug design: (a) PTS selectivity and (b) stability to amine oxidases. N-1,N-1'-[Naphthalene-1,4-diylbis(methylene)]bisN-4-[4-(methylamino)butyl])-butane-1,4-diamine}, 3b, was found to have an optimal balance between these parameters and demonstrated excellent targeting of melanoma (e.g., MALME-3M) and breast cancer cells (e.g., T47D) over other cancer cell lines. These results provide a method to selectively target cancers via their intrinsic need for polyamine metabolites.