5-{[5-acetylamino-2-(4-methoxybenzyl)-2H-pyrazole-3-carbonyl]-amino}-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid | 849599-57-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-{[5-acetylamino-2-(4-methoxybenzyl)-2H-pyrazole-3-carbonyl]-amino}-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid
• CAS: 849599-57-1
• 化学式: C₂₆H₂₆N₆O₆
• 分子量: 518.529
• InChiKey: HLWCESPSEPLYLY-UHFFFAOYSA-N

物化性质

• 熔点：
  110 °C
• 沸点：
  783.6±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  38.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  149.6
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5-{[5-acetylamino-2-(4-methoxybenzyl)-2H-pyrazole-3-carbonyl]-amino}-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic acid 在 2-氯-1-甲基吡啶碘化物 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 5-acetylamino-2H-pyrazole-3-carbonylamino-2H-pyrazole-3-carbonyl-(S)-lysinyl-(S)-valinyl-(S)-phenylalanine methyl ester tri(trifluoroacetate)
  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-乙酰氨基-2-(4-甲氧基苄基)-2H-吡唑-3-羧酸 在 lithium hydroxide 、 2-氯-1-甲基吡啶碘化物 、 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 16.0h， 生成 5-{[5-acetylamino-2-(4-methoxybenzyl)-2H-pyrazole-3-carbonyl]-amino}-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic 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

文献信息

• Synthesis and Binding Studies of Alzheimer Ligands on Solid Support
  作者：Petra Rzepecki、Nina Geib、Manuel Peifer、Frank Biesemeier、Thomas Schrader

  DOI：10.1021/jo061918x

  日期：2007.5.1

  Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed β-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure

  氨基吡唑衍生物构成第一类合理设计的非肽类β-折叠配体。在这里，我们描述了用于合成和亲和力测试的双重固相方案。所提出的四种杂合化合物的固相合成依赖于Fmoc策略，并通过从有机溶液中以纯净形式沉淀出最终产物来规避随后的HPLC纯化。具有内部二肽和四肽桥的六肽和八肽侧基现在可以高产率地用于化合物文库的组合合成，以进行高通量筛选。耐酸性PAM上的固相肽合成（SPPS）使我们在PMB脱保护后，可以将固定状态下的游离氨基吡唑结合位点进行荧光标记肽的珠上检测。从荧光发射强度的降低，可以通过简单地应用质量作用定律，通过参考曲线计算出各个结合常数。令人高兴的是，即使对于几乎不溶于水的那些配体，也可以定量地监测宿主/客体的复合。