Pyridine-2-carboxylic acid [(1S,2S)-1-benzyl-3-((S)-1-carbamoyl-3-methyl-butylamino)-2-hydroxy-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 [(1S,2S)-1-benzyl-3-((S)-1-carbamoyl-3-methyl-butylamino)-2-hydroxy-propyl]-amide
• 英文别名: Hydroxyethylamine-based inhibitor 6；N-[(2S,3S)-4-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-phenylbutan-2-yl]pyridine-2-carboxamide
• 化学式: C₂₂H₃₀N₄O₃
• 分子量: 398.505
• InChiKey: KIJVXDJZFILBNC-UFYCRDLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-吡啶甲酸 、 Fmoc-L-亮氨酸 、 (1S)-1-(2R)-环氧乙基-2-苯乙基氨基甲酸叔丁酯 以8%的产率得到Pyridine-2-carboxylic acid [(1S,2S)-1-benzyl-3-((S)-1-carbamoyl-3-methyl-butylamino)-2-hydroxy-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

文献信息

• Design and Synthesis of Plasmepsin I and Plasmepsin II Inhibitors with Activity in <i>Plasmodium </i><i>f</i><i>alciparum</i>-Infected Cultured Human Erythrocytes
  作者：Daniel Nöteberg、Elizabeth Hamelink、Johan Hultén、Mats Wahlgren、Lotta Vrang、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm020951i

  日期：2003.2.1

  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).