N-[(2S)-1-[[(2S,3S)-4-[(5S)-5-[(4-bromophenyl)methyl]-2,4-dioxoimidazolidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide | 500767-08-8

• 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: N-[(2S)-1-[[(2S,3S)-4-[(5S)-5-[(4-bromophenyl)methyl]-2,4-dioxoimidazolidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide
• CAS: 500767-08-8
• 化学式: C₃₁H₃₄BrN₅O₅
• 分子量: 636.545
• InChiKey: SJRJXOQQVRWRHA-FWEHEUNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(2S)-1-[[(2S,3S)-4-[(5S)-5-[(4-bromophenyl)methyl]-2,4-dioxoimidazolidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide 、 苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 生成 N-[(2S)-1-[[(2S,3S)-4-[(5S)-2,4-dioxo-5-[(4-phenylphenyl)methyl]imidazolidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide
  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
• 作为产物：
  描述：

  L-对溴苯丙氨酸甲酯 在 盐酸 、 氨 、 sodium carbonate 、 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 3.75h， 生成 N-[(2S)-1-[[(2S,3S)-4-[(5S)-5-[(4-bromophenyl)methyl]-2,4-dioxoimidazolidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide
  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).