di-tert-butyl [{[{[naphthalene-1,4-diylbis(methylene)]bis-(azanediyl)}bis(butane-4,1-diyl)]bis[(tert-butoxycarbonyl)-azanediyl]}bis(butane-4,1-diyl)]bis(methylcarbamate) | 1446751-83-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: di-tert-butyl [{[{[naphthalene-1,4-diylbis(methylene)]bis-(azanediyl)}bis(butane-4,1-diyl)]bis[(tert-butoxycarbonyl)-azanediyl]}bis(butane-4,1-diyl)]bis(methylcarbamate)
• 英文别名: di-tert-butyl (((((naphthalene-1,4-diylbis(methylene))bis(azanediyl))bis(butane-4,1-diyl))bis((tert-butoxycarbonyl)azanediyl))bis(butane-4,1-diyl))bis(methylcarbamate)；tert-butyl N-methyl-N-[4-[4-[[4-[[4-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butylamino]methyl]naphthalen-1-yl]methylamino]butyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl]carbamate
• CAS: 1446751-83-2
• 化学式: C₅₀H₈₆N₆O₈
• 分子量: 899.268
• InChiKey: CWRMGSQGVVHRRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  64
• 可旋转键数：
  32
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 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 [{[{[naphthalene-1,4-diylbis(methylene)]bis-(azanediyl)}bis(butane-4,1-diyl)]bis[(tert-butoxycarbonyl)-azanediyl]}bis(butane-4,1-diyl)]bis(methylcarbamate) 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以98%的产率得到N¹,N¹ ′-[naphthalene-1,4-diylbis(methylene)]bis{N⁴-[4-(methylamino)butyl]butane-1,4-diamine}
  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 盐酸 、 sodium tetrahydroborate 、 potassium carbonate 、 sodium sulfate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 6.83h， 生成 di-tert-butyl [{[{[naphthalene-1,4-diylbis(methylene)]bis-(azanediyl)}bis(butane-4,1-diyl)]bis[(tert-butoxycarbonyl)-azanediyl]}bis(butane-4,1-diyl)]bis(methylcarbamate)
  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

文献信息

• 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.