(2S,5S,6S)-3-aza-3-(benzyloxycarbonyl)-2-(p-bromobenzyl)-6-[[(tert-butyloxycarbonyl)-L-valinyl]amino]-5-hydroxy-7-phenylheptanoyl amide | 558467-56-4

• 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: (2S,5S,6S)-3-aza-3-(benzyloxycarbonyl)-2-(p-bromobenzyl)-6-[[(tert-butyloxycarbonyl)-L-valinyl]amino]-5-hydroxy-7-phenylheptanoyl amide
• 英文别名: benzyl N-[(2S)-1-amino-3-(4-bromophenyl)-1-oxopropan-2-yl]-N-[(2S,3S)-2-hydroxy-3-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-4-phenylbutyl]carbamate
• CAS: 558467-56-4
• 化学式: C₃₇H₄₇BrN₄O₇
• 分子量: 739.707
• InChiKey: ZMWKPBKGEGJUMX-YDPTYEFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  49
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,5S,6S)-3-aza-3-(benzyloxycarbonyl)-2-(p-bromobenzyl)-6-[[(tert-butyloxycarbonyl)-L-valinyl]amino]-5-hydroxy-7-phenylheptanoyl amide 在 盐酸 、 三氟甲磺酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 生成 Hydroxyethylamine-based inhibitor 11f
  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 、 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 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 0.5h， 生成 (2S,5S,6S)-3-aza-3-(benzyloxycarbonyl)-2-(p-bromobenzyl)-6-[[(tert-butyloxycarbonyl)-L-valinyl]amino]-5-hydroxy-7-phenylheptanoyl 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