ethyl 6-(N-benzoylbenzamido)-2-methyl-2H-pyrazolo[3,4-d]pyrimidine-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 6-(N-benzoylbenzamido)-2-methyl-2H-pyrazolo[3,4-d]pyrimidine-4-carboxylate
• 英文别名: Ethyl 6-(dibenzoylamino)-2-methylpyrazolo[3,4-d]pyrimidine-4-carboxylate；ethyl 6-(dibenzoylamino)-2-methylpyrazolo[3,4-d]pyrimidine-4-carboxylate
• 化学式: C₂₃H₁₉N₅O₄
• 分子量: 429.435
• InChiKey: BOYCMKKNTHYKDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-amino-2-methyl-2H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 在 硫酸 、 双氧水 、 potassium carbonate 、 N,N-二甲基苯胺 、 sodium 4-methylbenzenesulfinate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 63.0h， 生成 ethyl 6-(N-benzoylbenzamido)-2-methyl-2H-pyrazolo[3,4-d]pyrimidine-4-carboxylate
  参考文献：
  名称：

  A facile and novel synthesis of N2-, C6-substituted pyrazolo[3,4-d]pyrimidine-4 carboxylate derivatives as adenosine receptor antagonists

  摘要：

  An efficient synthetic procedure was adopted to synthesize a series of new molecules containing the pyrazolo[3,4-d]pyrimidine (PP) scaffold, which have been evaluated as promising human adenosine receptor (AR) antagonists. The effect of substitutions at the N-2, C-4 and C-6 positions of PPs on the affinity and selectivity towards the adenosine receptors were explored. Most of the pyrazolo[3,4-d]pyrimidine-4-carboxylates displayed from moderate to good affinity at the human A(3)AR (hA(3)AR), as indicated by the low micromolar range of K-i values (K-i hA(3)AR = 0.7-34 mu M). In particular, compounds 60 and 62 displayed good affinity at the hA(3)AR (60, K-i hA(3)AR = 2.2 mu M and 62, K-i hA(3)AR = 2.9 mu M) and selectivity towards the other AR subtypes (60, >46-fold selective and 62, >34-fold selective, respectively). In view of these results, these novel PP analogues were docked both in the crystallographic structure of the hA(2A)AR and in a homology model of the hA(3)AR in order to support the structure activity relationship (SAR) analysis. These preliminary results demonstrated that pyrazolo[3,4-d]pyrimidine can be considered a promising scaffold to obtain new molecules with potent hA(3)AR antagonist activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.046

文献信息

• A facile and novel synthesis of N2-, C6-substituted pyrazolo[3,4-d]pyrimidine-4 carboxylate derivatives as adenosine receptor antagonists
  作者：G. Venkatesan、P. Paira、S.L. Cheong、S. Federico、K.N. Klotz、G. Spalluto、G. Pastorin

  DOI：10.1016/j.ejmech.2015.01.046

  日期：2015.3

  An efficient synthetic procedure was adopted to synthesize a series of new molecules containing the pyrazolo[3,4-d]pyrimidine (PP) scaffold, which have been evaluated as promising human adenosine receptor (AR) antagonists. The effect of substitutions at the N-2, C-4 and C-6 positions of PPs on the affinity and selectivity towards the adenosine receptors were explored. Most of the pyrazolo[3,4-d]pyrimidine-4-carboxylates displayed from moderate to good affinity at the human A(3)AR (hA(3)AR), as indicated by the low micromolar range of K-i values (K-i hA(3)AR = 0.7-34 mu M). In particular, compounds 60 and 62 displayed good affinity at the hA(3)AR (60, K-i hA(3)AR = 2.2 mu M and 62, K-i hA(3)AR = 2.9 mu M) and selectivity towards the other AR subtypes (60, >46-fold selective and 62, >34-fold selective, respectively). In view of these results, these novel PP analogues were docked both in the crystallographic structure of the hA(2A)AR and in a homology model of the hA(3)AR in order to support the structure activity relationship (SAR) analysis. These preliminary results demonstrated that pyrazolo[3,4-d]pyrimidine can be considered a promising scaffold to obtain new molecules with potent hA(3)AR antagonist activity. (C) 2015 Elsevier Masson SAS. All rights reserved.