2-(4-Benzyloxy-benzyl)-4-(5-furan-2-yl-2H-[1,2,4]triazol-3-yl)-2H-pyrazol-3-ylamine | 207233-81-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-Benzyloxy-benzyl)-4-(5-furan-2-yl-2H-[1,2,4]triazol-3-yl)-2H-pyrazol-3-ylamine
• 英文别名: 4-[5-(furan-2-yl)-1H-1,2,4-triazol-3-yl]-2-[(4-phenylmethoxyphenyl)methyl]pyrazol-3-amine
• CAS: 207233-81-6
• 化学式: C₂₃H₂₀N₆O₂
• 分子量: 412.451
• InChiKey: HZVWRTMZLMZWFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-Benzyloxy-benzyl)-4-(5-furan-2-yl-2H-[1,2,4]triazol-3-yl)-2H-pyrazol-3-ylamine 在 palladium on activated charcoal N-甲基吡咯烷酮 、 氢气 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 25.0~160.0 ℃ 、344.73 kPa 条件下， 反应 4.0h， 生成 5-amino-7-[4-hydroxybenzyl]-2-(furan-2-yl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

  摘要：

  New A(2A) adenosine receptor antagonists in the series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A(2A) compared to rat A(1) and human A(3) receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A(1) and A(2A) adenosine receptors. They showed very good affinity (K-i = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA(1) and hA(3) (compound 5h: rA(1)/rA(2A) = 787, hA(3)/rA(2A) > 10000) These important findings make this new series of compounds the first really selective for A(2A) adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

  DOI：

  10.1021/jm9708689
• 作为产物：
  描述：

  2-呋喃甲酰肼 在 盐酸 作用下， 反应 4.5h， 生成 2-(4-Benzyloxy-benzyl)-4-(5-furan-2-yl-2H-[1,2,4]triazol-3-yl)-2H-pyrazol-3-ylamine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

  摘要：

  New A(2A) adenosine receptor antagonists in the series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A(2A) compared to rat A(1) and human A(3) receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A(1) and A(2A) adenosine receptors. They showed very good affinity (K-i = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA(1) and hA(3) (compound 5h: rA(1)/rA(2A) = 787, hA(3)/rA(2A) > 10000) These important findings make this new series of compounds the first really selective for A(2A) adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

  DOI：

  10.1021/jm9708689