4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-2-N-(2-methylpropyl)-6-phenylpyrimidine-2,4-diamine | 1440426-42-5

• 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: 4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-2-N-(2-methylpropyl)-6-phenylpyrimidine-2,4-diamine
• CAS: 1440426-42-5
• 化学式: C₂₀H₂₆N₈
• 分子量: 378.48
• InChiKey: BWABJYLJTJRZRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  114
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 5%-palladium/activated carbon 、 氢气 、 palladium(II) hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 水 为溶剂， 20.0~130.0 ℃ 、400.01 kPa 条件下， 反应 121.0h， 生成 4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-2-N-(2-methylpropyl)-6-phenylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Bispyrimidines as Potent Histamine H₄ Receptor Ligands: Delineation of Structure–Activity Relationships and Detailed H₄ Receptor Binding Mode

  摘要：

  The basic methylpiperazine moiety is considered a necessary substructure for high histamine H-4 receptor (H4R) affinity. This moiety is however also the metabolic hot spot for various classes of H4R ligands (e.g., indolcarboxamides and pyrimidines). We set out to investigate whether mildly basic 2-aminopyrimidines in combination with the appropriate linker can serve as a replacement for the methylpiperazine moiety. In the series of 2-aminopyrimidines, the introduction of an additional 2-aminopyrimidine moiety in combination with the appropriate linker lead to bispyrimidines displaying pK(i) values for binding the human H4R up to 8.2. Furthermore, the methylpiperazine replacement results in compounds with improved metabolic properties. The attempt to transfer the knowledge generated in the class of bispyrimidines to the indolecarboxamides failed. Combining the derived structure-activity relationships with homology modeling leads to new detailed insights in the molecular aspects of ligand-H4R binding in general and the binding mode of the described bispyrimidines in specific.

  DOI：

  10.1021/jm301886t

文献信息

• H4 RECEPTOR INHIBITORS FOR TREATING TINNITUS
  申请人：Sensorion

  公开号：EP3378476A1

  公开（公告）日：2018-09-26

  The invention relates to Histamine type 4 receptor (H4R) inhibitors for treating tinnitus.

  本发明涉及用于治疗耳鸣的组胺 4 型受体（H4R）抑制剂。
• US9688989B2
  申请人：——

  公开号：US9688989B2

  公开（公告）日：2017-06-27