3,3'-(4,4'-(ethane-1,1-diyl)bis(2,6-dibromo-4,1-phenylene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol) | 1239516-82-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,3'-(4,4'-(ethane-1,1-diyl)bis(2,6-dibromo-4,1-phenylene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol)
• 英文别名: 1-[2,6-Dibromo-4-[1-[3,5-dibromo-4-[2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy]phenyl]ethyl]phenoxy]-3-(4-methylpiperazin-1-yl)propan-2-ol
• CAS: 1239516-82-5
• 化学式: C₃₀H₄₂Br₄N₄O₄
• 分子量: 842.304
• InChiKey: MCOBOFAYSPSCNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  71.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 2,2'-(4,4'-(ethane-1,1-diyl)bis(2,6-dibromo-4,1-phenylene))bis-(oxy)bis(methylene)dioxirane 在 甲醇 作用下， 反应 3.0h， 以78%的产率得到3,3'-(4,4'-(ethane-1,1-diyl)bis(2,6-dibromo-4,1-phenylene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol)
  参考文献：
  名称：

  Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as β-Amyloid Peptide Aggregation Inhibitors

  摘要：

  The aggregation of A beta is a crucial step in the etiology of Alzheimer's disease. Our previous work showed that A beta undergoes alpha-helix/beta-sheet intermediate structures during the conformational transition, and an A beta aggregation inhibitor (1) was discovered by targeting the intermediates. Here, structure optimization toward compound 1 was performed and 34 novel derivatives were designed and synthesized. Nine compounds showed more effective inhibitory activity than the hit compound 1 in ThT fluorescence assay. Among them, compound 43 demonstrated more excellent inhibitory potency, which not only can suppress the aggregation of A beta but also can dissolve the preformed fibrils as shown by CD spectroscopy, PICUP and AFM assays. Cellular assay indicated that 43 has no toxicity to neuronal cells, moreover, can effectively inhibit A beta(1-42)-induced neutrotoxicity and increase the cell viability. Together, on the basis of these positive results, these novel chemical structures may provide a promising potential for therapeutic applications in AD and other types of neurodegenerative disorders.

  DOI：

  10.1021/jm1000584