Pyridine-2-carboxylic acid ((S)-1-{(1S,2S)-1-benzyl-3-[((S)-carbamoyl-phenyl-methyl)-amino]-2-hydroxy-propylcarbamoyl}-2-methyl-propyl)-amide

• 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: Pyridine-2-carboxylic acid ((S)-1-{(1S,2S)-1-benzyl-3-[((S)-carbamoyl-phenyl-methyl)-amino]-2-hydroxy-propylcarbamoyl}-2-methyl-propyl)-amide
• 英文别名: Hydroxyethylamine-based inhibitor 11c；N-[(2S)-1-[[(2S,3S)-4-[[(1S)-2-amino-2-oxo-1-phenylethyl]amino]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide
• 化学式: C₂₉H₃₅N₅O₄
• 分子量: 517.628
• InChiKey: HQJDPWUHNHPHKG-CQJMVLFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ((S)-Carbamoyl-phenyl-methyl)-((2S,3S)-2-hydroxy-3-{(S)-3-methyl-2-[(pyridine-2-carbonyl)-amino]-butyrylamino}-4-phenyl-butyl)-carbamic acid benzyl ester 在 ammonium formate 作用下， 以 乙醇 为溶剂， 以120 mg的产率得到Pyridine-2-carboxylic acid ((S)-1-{(1S,2S)-1-benzyl-3-[((S)-carbamoyl-phenyl-methyl)-amino]-2-hydroxy-propylcarbamoyl}-2-methyl-propyl)-amide
  参考文献：
  名称：

  Design and Synthesis of Plasmepsin I and Plasmepsin II Inhibitors with Activity in Plasmodium falciparum-Infected Cultured Human Erythrocytes

  摘要：

  A series of protease inhibitors targeted at the malarial enzymes plasmepsin I and II, and encompassing a basic hydroxyethylamine transition state isostere scaffold, was prepared. The substituents in the P1' position were varied and the biological activities expressed in K-i-values ranged from 60 to > 2000 nM. A more than 4-fold selectivity for either of the plasmepsins could be achieved. All of the active compounds exhibited high preference for the plasmepsins over cathepsin D, the most closely related human protease. A few active compounds were shown to inhibit parasite growth in cultured infected human erythrocytes. An ED50 value as low as 1.6 muM was observed for one of the inhibitors despite K-i values of 115 nM (Plm I) and 121 nM (Plm II).

  DOI：

  10.1021/jm020951i