| 1533410-83-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• CAS: 1533410-83-1
• 化学式: C₃₂H₅₄N₄O₇
• 分子量: 606.803
• InChiKey: BTPLVTUKBSCAET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.37
• 重原子数：
  43.0
• 可旋转键数：
  14.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  130.0
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  在 3-氯苯甲酰乙腈 、 sodium carbonate 作用下， 反应 2.0h， 以45%的产率得到2-甲基-2-丙基(3-氨基丙基)[4-({[(2-甲基-2-丙基)氧基]羰基}[3-({[(2-甲基-2-丙基)氧基]羰基}氨基)丙基]氨基)丁基]氨基甲酸酯
  参考文献：
  名称：

  Polyamine Transport Inhibitors: Design, Synthesis, and Combination Therapies with Difluoromethylornithine

  摘要：

  The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N-1,N-1',N-1 ''-(benzene-1,3,5-triyltris(methylene))tris(N-4-(4-(methylamino)butyl)butane-1,4-diamine, 6b, which contained three N-methylhomospermidine motifs. This PTI exhibited decreased sensitivity to amine oxidases and low toxicity as well as high potency (EC50 = 1.4 mu M) in inhibiting the uptake of spermidine (1 mu M) in DFMO-treated L3.6pl human pancreatic cancer cells.

  DOI：

  10.1021/jm401174a
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 2-(((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)imino)methyl)phenol 反应 1.5h， 生成
  参考文献：
  名称：

  Polyamine Transport Inhibitors: Design, Synthesis, and Combination Therapies with Difluoromethylornithine

  摘要：

  The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N-1,N-1',N-1 ''-(benzene-1,3,5-triyltris(methylene))tris(N-4-(4-(methylamino)butyl)butane-1,4-diamine, 6b, which contained three N-methylhomospermidine motifs. This PTI exhibited decreased sensitivity to amine oxidases and low toxicity as well as high potency (EC50 = 1.4 mu M) in inhibiting the uptake of spermidine (1 mu M) in DFMO-treated L3.6pl human pancreatic cancer cells.

  DOI：

  10.1021/jm401174a