4,6-di(benzo[d][1,3]dioxol-5-yl)pyrimidin-2-amine | 1262324-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 4,6-di(benzo[d][1,3]dioxol-5-yl)pyrimidin-2-amine
• 英文别名: 4,6-Bis(1,3-benzodioxol-5-yl)pyrimidin-2-amine
• CAS: 1262324-12-8
• 化学式: C₁₈H₁₃N₃O₄
• 分子量: 335.319
• InChiKey: SODMOKBGYBWECS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  88.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-4,6-二氯嘧啶 、 3.4-(亚甲基二氧基)苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 12.0h， 以67%的产率得到4,6-di(benzo[d][1,3]dioxol-5-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Pyrimidine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists

  摘要：

  Two regioisomeric series of diaryl 2- or 4-amidopyrimidines have been synthesized and their adenosine receptor affinities were determined in radioligand binding assays at the four human adenosine receptors (hARs). Some of the ligands prepared herein exhibit remarkable affinities (K-i < 10 nm) and, most noticeably, the absence of activity at the A(1), A(2A), and A(2B) receptors. The structural determinants that support the affinity and selectivity profiles of the series were highlighted through an integrated computational approach, combining a 3D-QSAR model built on the second generation of G Rid INdependent Descriptors (GRIND2) with a novel homology model of the hA(3) receptor. The robustness of the computational model was subsequently evaluated by the design of new derivatives exploring the alkyl substituent of the exocyclic amide group. The synthesis and evaluation of the novel compounds validated the predictive power of the model, exhibiting excellent agreement between predicted and experimental activities.

  DOI：

  10.1021/jm100843z

文献信息

• Pyrimidine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists
  作者：Vicente Yaziji、David Rodríguez、Hugo Gutiérrez-de-Terán、Alberto Coelho、Olga Caamaño、Xerardo García-Mera、José Brea、María Isabel Loza、María Isabel Cadavid、Eddy Sotelo

  DOI：10.1021/jm100843z

  日期：2011.1.27

  Two regioisomeric series of diaryl 2- or 4-amidopyrimidines have been synthesized and their adenosine receptor affinities were determined in radioligand binding assays at the four human adenosine receptors (hARs). Some of the ligands prepared herein exhibit remarkable affinities (K-i < 10 nm) and, most noticeably, the absence of activity at the A(1), A(2A), and A(2B) receptors. The structural determinants that support the affinity and selectivity profiles of the series were highlighted through an integrated computational approach, combining a 3D-QSAR model built on the second generation of G Rid INdependent Descriptors (GRIND2) with a novel homology model of the hA(3) receptor. The robustness of the computational model was subsequently evaluated by the design of new derivatives exploring the alkyl substituent of the exocyclic amide group. The synthesis and evaluation of the novel compounds validated the predictive power of the model, exhibiting excellent agreement between predicted and experimental activities.