4,4'-(pentane-1,5-diylbis(oxy))bis(N-(5-aminopentyl)-benzimidamide)

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4,4'-(pentane-1,5-diylbis(oxy))bis(N-(5-aminopentyl)-benzimidamide)
• 英文别名: N'-(5-aminopentyl)-4-[5-[4-[N'-(5-aminopentyl)carbamimidoyl]phenoxy]pentoxy]benzenecarboximidamide
• 化学式: C₂₉H₄₆N₆O₂
• 分子量: 510.723
• InChiKey: IYWFQSSPAARIAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  37
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,5-二(4-氰基苯氧基)戊烷 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4,4'-(pentane-1,5-diylbis(oxy))bis(N-(5-aminopentyl)-benzimidamide)
  参考文献：
  名称：

  Small Molecule Inhibitors of Ca²⁺-S100B Reveal Two Protein Conformations

  摘要：

  The drug pentamidine inhibits calcium-dependent complex formation with p53 ((Ca)S100Bp53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure-activity relationship (SAR) studies were therefore completed here with 23 pentamidine analogues, and X-ray structures of (Ca)S100Binhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the FF-gate. For symmetric pentamidine analogues ((Ca)S100B5a, (Ca)S100B6b) a channel between sites 1 and 2 on S100B was occluded by residue Phe88, but for an asymmetric pentamidine analogue ((Ca)S100B17), this same channel was open. The (Ca)S100B17 structure illustrates, for the first time, a pentamidine analog capable of binding the open form of the FF-gate and provides a means to block all three hot spots on (Ca)S100B, which will impact next generation (Ca)S100Bp53 inhibitor design.

  DOI：

  10.1021/acs.jmedchem.5b01369