1,5-bis(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)-pentane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1,5-bis(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)-pentane
• 英文别名: 2,2'-[pentane-1,5-Diylbis(Oxybenzene-4,1-Diyl)]di-1,4,5,6-Tetrahydropyrimidine；2-[4-[5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]pentoxy]phenyl]-1,4,5,6-tetrahydropyrimidine
• 化学式: C₂₅H₃₂N₄O₂
• 分子量: 420.555
• InChiKey: KPYLNHFSSDNDFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

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 1,5-bis(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)-pentane
  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

文献信息

• [EN] ANTIFUNGAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIFONGIQUES
  申请人：MICROBIOTIX INC

  公开号：WO2013052263A2

  公开（公告）日：2013-04-11

  The invention provides fungicide and/or antifungal organic compounds and compositions thereof that kill or inhibit growth of cells of one or more microbial pathogens.
• Small Molecule Inhibitors of Ca²⁺-S100B Reveal Two Protein Conformations
  作者：Michael C. Cavalier、Mohd. Imran Ansari、Adam D. Pierce、Paul T. Wilder、Laura E. McKnight、E. Prabhu Raman、David B. Neau、Padmavani Bezawada、Milad J. Alasady、Thomas H. Charpentier、Kristen M. Varney、Eric A. Toth、Alexander D. MacKerell、Andrew Coop、David J. Weber

  DOI：10.1021/acs.jmedchem.5b01369

  日期：2016.1.28

  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.