N-benzyloxycarbonyl-Nε-(tert-butyloxycarbonyl)-(S)-lysinyl-(S)-valinyl-5-amino-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid methyl ester | 849599-82-2

• 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-benzyloxycarbonyl-Nε-(tert-butyloxycarbonyl)-(S)-lysinyl-(S)-valinyl-5-amino-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid methyl ester
• 英文别名: N-benzyloxycarbonyl-N^ε-(tert-butyloxycarbonyl)-(S)-lysinyl-(S)-valinyl-5-amino-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid methyl ester
• CAS: 849599-82-2
• 化学式: C₃₇H₅₀N₆O₉
• 分子量: 722.839
• InChiKey: DSKJWYLBCDJPCU-IZEXYCQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  52.0
• 可旋转键数：
  17.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  188.21
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-Nε-(tert-butyloxycarbonyl)-(S)-lysinyl-(S)-valinyl-5-amino-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid methyl ester 在 palladium on activated charcoal 2-氯-1-甲基吡啶碘化物 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 5-((S)-2-{(S)-6-Amino-2-[(5-{2-[2-(2-methoxy-ethoxy)-ethoxy]-acetylamino}-2H-pyrazole-3-carbonyl)-amino]-hexanoylamino}-3-methyl-butyrylamino)-2H-pyrazole-3-carboxylic acid methyl ester; compound with trifluoro-acetic acid
  参考文献：
  名称：

  β-Sheet Ligands in Action:  KLVFF Recognition by Aminopyrazole Hybrid Receptors in Water

  摘要：

  Little is known about the precise mechanism of action of beta-sheet ligands, hampered by the notorious solubility problems involved with protein misfolding and amyloid formation. Recently the nucleation site for the pathogenic aggregation of the Alzheimer's peptide was identified as the KLVFF sequence in the central region of Abeta. A combination of two aminopyrazole ligands with di- or tripepticles taken from this key fragment now furnished water-soluble Abeta-specific ligands which allow model investigations in water. A detailed conformational analysis provides experimental evidence for an increased -sheet content induced in the peptide. Strong indications were also found for the peptide backbone recognition via hydrogen bonds plus hydrophobic contributions between aminopyrazole nuclei and Phe residues. The affinity of these new ligands toward the KKLVFF fragment is highly dependent on their sequence and composition from natural and artificial amino acids. Thus, for the first time, detailed insight is gained into the complexation of beta-sheet ligands with model peptices taken directly from Abeta.

  DOI：

  10.1021/ja045558b
• 作为产物：
  描述：

  5-amino-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid methyl ester 在 2,6-二甲基吡啶 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 6-氯-1-羟基苯并三氮唑 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.34h， 生成 N-benzyloxycarbonyl-Nε-(tert-butyloxycarbonyl)-(S)-lysinyl-(S)-valinyl-5-amino-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid methyl ester
  参考文献：
  名称：

  β-Sheet Ligands in Action:  KLVFF Recognition by Aminopyrazole Hybrid Receptors in Water

  摘要：

  Little is known about the precise mechanism of action of beta-sheet ligands, hampered by the notorious solubility problems involved with protein misfolding and amyloid formation. Recently the nucleation site for the pathogenic aggregation of the Alzheimer's peptide was identified as the KLVFF sequence in the central region of Abeta. A combination of two aminopyrazole ligands with di- or tripepticles taken from this key fragment now furnished water-soluble Abeta-specific ligands which allow model investigations in water. A detailed conformational analysis provides experimental evidence for an increased -sheet content induced in the peptide. Strong indications were also found for the peptide backbone recognition via hydrogen bonds plus hydrophobic contributions between aminopyrazole nuclei and Phe residues. The affinity of these new ligands toward the KKLVFF fragment is highly dependent on their sequence and composition from natural and artificial amino acids. Thus, for the first time, detailed insight is gained into the complexation of beta-sheet ligands with model peptices taken directly from Abeta.

  DOI：

  10.1021/ja045558b