2-amino-6-(2,6-dimethoxyphenyl)-9H-purine

• 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: 2-amino-6-(2,6-dimethoxyphenyl)-9H-purine
• 英文别名: 6-(2,6-dimethoxyphenyl)-7H-purin-2-amine
• 化学式: C₁₃H₁₃N₅O₂
• 分子量: 271.279
• InChiKey: KVDHOOWLSZIDSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  98.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,6-二甲氧基苯硼酸 、 2-氨基-6-溴嘌呤 在 palladium diacetate 、 caesium carbonate 作用下， 以 水 、 乙腈 为溶剂， 以53%的产率得到2-amino-6-(2,6-dimethoxyphenyl)-9H-purine
  参考文献：
  名称：

  9H-Purine Scaffold Reveals Induced-Fit Pocket Plasticity of the BRD9 Bromodomain

  摘要：

  The 2-amine-9H-purine scaffold was identified as a weak bromodomain template and was developed via iterative structure based design into a potent nanomolar ligand for the bromodomain of human BRD9 with small residual micromolar affinity toward the bromodomain of BRD4. Binding of the lead compound 11 to the bromodomain of BRD9 results in an unprecedented rearrangement of residues forming the acetyllysine recognition site, affecting plasticity of the protein in an induced-fit pocket. The compound does not exhibit any cytotoxic effect in HEK293 cells and displaces the BRD9 bromodomain from chromatin in bioluminescence proximity assays without affecting the BRD4/histone complex. The 2-amine-9H-purine scaffold represents a novel template that can be further modified to yield highly potent and selective tool compounds to interrogate the biological role of BRD9 in diverse cellular systems.

  DOI：

  10.1021/jm501893k

文献信息

• 9<i>H</i>-Purine Scaffold Reveals Induced-Fit Pocket Plasticity of the BRD9 Bromodomain
  作者：Sarah Picaud、Maria Strocchia、Stefania Terracciano、Gianluigi Lauro、Jacqui Mendez、Danette L. Daniels、Raffaele Riccio、Giuseppe Bifulco、Ines Bruno、Panagis Filippakopoulos

  DOI：10.1021/jm501893k

  日期：2015.3.26

  The 2-amine-9H-purine scaffold was identified as a weak bromodomain template and was developed via iterative structure based design into a potent nanomolar ligand for the bromodomain of human BRD9 with small residual micromolar affinity toward the bromodomain of BRD4. Binding of the lead compound 11 to the bromodomain of BRD9 results in an unprecedented rearrangement of residues forming the acetyllysine recognition site, affecting plasticity of the protein in an induced-fit pocket. The compound does not exhibit any cytotoxic effect in HEK293 cells and displaces the BRD9 bromodomain from chromatin in bioluminescence proximity assays without affecting the BRD4/histone complex. The 2-amine-9H-purine scaffold represents a novel template that can be further modified to yield highly potent and selective tool compounds to interrogate the biological role of BRD9 in diverse cellular systems.