(3S,4S)-4-azido-3-hydroxy-6-phenylhexanoic acid [(S)-1-((S)-1-carbamoyl-3-methylbutylcarbamoyl)ethyl]amide | 724733-52-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,4S)-4-azido-3-hydroxy-6-phenylhexanoic acid [(S)-1-((S)-1-carbamoyl-3-methylbutylcarbamoyl)ethyl]amide
• CAS: 724733-52-2
• 化学式: C₂₁H₃₂N₆O₄
• 分子量: 432.523
• InChiKey: KXQOQEWFBHDCOQ-DKIMLUQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.57
• 重原子数：
  31.0
• 可旋转键数：
  13.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  170.28
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (3S,4S)-4-azido-3-hydroxy-6-phenylhexanoic acid [(S)-1-((S)-1-carbamoyl-3-methylbutylcarbamoyl)ethyl]amide 在 水 、 三苯基膦 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Design and Synthesis of Potent Inhibitors of the Malaria Aspartyl Proteases Plasmepsin I and II. Use of Solid-Phase Synthesis to Explore Novel Statine Motifs

  摘要：

  Picomolar to low nanomolar inhibitors of the two aspartic proteases plasmepsin (Plm) I and II, from the malaria parasite Plasmodium falciparum, have been identified from sets of libraries containing novel statine-like templates modified at the amino and carboxy terminus. The syntheses of the novel statine templates were carried out in solution phase using efficient synthetic routes and resulting in excellent stereochemical control. The most promising statine template was attached to solid support and diversified by use of parallel synthesis. The products were evaluated for their Plm I and II inhibitory activity as well as their selectivity over cathepsin D. Selected inhibitors were, in addition, evaluated for their inhibition of parasite growth in cultured infected human red blood cells. The most potent inhibitor in this report, compound 16, displays K-i values of 0.5 and 2.2 nM for Plm I and II, respectively. Inhibitor 16 is also effective in attenuating parasite growth in red blood cells showing 51% inhibition at a concentration of 5 muM. Several inhibitors have been identified that exhibit K-i values between 0.5 and 74 nM for both Plm I and II. Some of these inhibitors also show excellent selectivity vs cathepsin D.

  DOI：

  10.1021/jm031106i
• 作为产物：
  描述：

  Z-(S)-Ala-(S)-Leu-NH2 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (3S,4S)-4-azido-3-hydroxy-6-phenylhexanoic acid [(S)-1-((S)-1-carbamoyl-3-methylbutylcarbamoyl)ethyl]amide
  参考文献：
  名称：

  Design and Synthesis of Potent Inhibitors of the Malaria Aspartyl Proteases Plasmepsin I and II. Use of Solid-Phase Synthesis to Explore Novel Statine Motifs

  摘要：

  Picomolar to low nanomolar inhibitors of the two aspartic proteases plasmepsin (Plm) I and II, from the malaria parasite Plasmodium falciparum, have been identified from sets of libraries containing novel statine-like templates modified at the amino and carboxy terminus. The syntheses of the novel statine templates were carried out in solution phase using efficient synthetic routes and resulting in excellent stereochemical control. The most promising statine template was attached to solid support and diversified by use of parallel synthesis. The products were evaluated for their Plm I and II inhibitory activity as well as their selectivity over cathepsin D. Selected inhibitors were, in addition, evaluated for their inhibition of parasite growth in cultured infected human red blood cells. The most potent inhibitor in this report, compound 16, displays K-i values of 0.5 and 2.2 nM for Plm I and II, respectively. Inhibitor 16 is also effective in attenuating parasite growth in red blood cells showing 51% inhibition at a concentration of 5 muM. Several inhibitors have been identified that exhibit K-i values between 0.5 and 74 nM for both Plm I and II. Some of these inhibitors also show excellent selectivity vs cathepsin D.

  DOI：

  10.1021/jm031106i