(2R)-2-[(2E)-3-bromo-2-propenyloxy]-2-{(2R,3R,4R)-4-[(2E)-3-bromo-2-propenyloxy]-3-hydroxy-5-oxo-tetrahydrofuran-2-yl}-1N-(2-hydroxyindan-1-yl)ethanamide | 866755-90-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R)-2-[(2E)-3-bromo-2-propenyloxy]-2-{(2R,3R,4R)-4-[(2E)-3-bromo-2-propenyloxy]-3-hydroxy-5-oxo-tetrahydrofuran-2-yl}-1N-(2-hydroxyindan-1-yl)ethanamide
• CAS: 866755-90-0
• 化学式: C₂₁H₂₃Br₂NO₇
• 分子量: 561.224
• InChiKey: XRGWTWPZHXAMBB-XBNDTTROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.63
• 重原子数：
  31.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  114.32
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (2R)-2-[(2E)-3-bromo-2-propenyloxy]-2-{(2R,3R,4R)-4-[(2E)-3-bromo-2-propenyloxy]-3-hydroxy-5-oxo-tetrahydrofuran-2-yl}-1N-(2-hydroxyindan-1-yl)ethanamide 在 伯吉斯试剂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2R,3S,4S,5R)-5-(5-Benzyl-[1,3,4]oxadiazol-2-yl)-2,5-bis-((E)-3-bromo-allyloxy)-3,4-bis-trimethylsilanyloxy-pentanoic acid ((1S,2R)-2-trimethylsilanyloxy-indan-1-yl)-amide
  参考文献：
  名称：

  Synthesis of Malarial Plasmepsin Inhibitors and Prediction of Binding Modes by Molecular Dynamics Simulations

  摘要：

  A series of inhibitors of the malarial aspartic proteases Plm I and II have been synthesized with L-mannitol as precursor. These inhibitors are characterized by either a diacylhydrazine or a five-membered oxadiazole ring replacing backbone amide functionalities. Molecular dynamics simulations were applied in the design process. The computationally predicted Plm II K-i values were generally in excellent agreement with the biological results. The diacylhydrazine was found to be superior over the oxadiazole as an amide bond replacement in the Plm I and II inhibitors studied. An extensive flexibility of the S2 ' pocket was captured by the simulations predicting the binding mode of the unsymmetrical inhibitors. Plm I and II inhibitors with single digit nanomolar K-i values devoid of inhibitory activity toward human Cat D were identified. One compound, lacking amide bonds, was found to be Plm IV selective and very potent, with a K-i value of 35 nM.

  DOI：

  10.1021/jm050463l
• 作为产物：
  描述：

  (1S,2R)-(-)-1-氨基-2-茚醇 、 2,5-O-bis((2E)-3-bromo-2-propen-1-yl)-L-mannaro-1,4:3,6-di-γ-lactone 在 2-羟基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以44%的产率得到(2R)-2-[(2E)-3-bromo-2-propenyloxy]-2-{(2R,3R,4R)-4-[(2E)-3-bromo-2-propenyloxy]-3-hydroxy-5-oxo-tetrahydrofuran-2-yl}-1N-(2-hydroxyindan-1-yl)ethanamide
  参考文献：
  名称：

  Synthesis of Malarial Plasmepsin Inhibitors and Prediction of Binding Modes by Molecular Dynamics Simulations

  摘要：

  A series of inhibitors of the malarial aspartic proteases Plm I and II have been synthesized with L-mannitol as precursor. These inhibitors are characterized by either a diacylhydrazine or a five-membered oxadiazole ring replacing backbone amide functionalities. Molecular dynamics simulations were applied in the design process. The computationally predicted Plm II K-i values were generally in excellent agreement with the biological results. The diacylhydrazine was found to be superior over the oxadiazole as an amide bond replacement in the Plm I and II inhibitors studied. An extensive flexibility of the S2 ' pocket was captured by the simulations predicting the binding mode of the unsymmetrical inhibitors. Plm I and II inhibitors with single digit nanomolar K-i values devoid of inhibitory activity toward human Cat D were identified. One compound, lacking amide bonds, was found to be Plm IV selective and very potent, with a K-i value of 35 nM.

  DOI：

  10.1021/jm050463l