4-N-(2-aminoethyl)-6-phenylpyrimidine-2,4-diamine | 1440426-62-9

• 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-aminoethyl)-6-phenylpyrimidine-2,4-diamine
• CAS: 1440426-62-9
• 化学式: C₁₂H₁₅N₅
• 分子量: 229.285
• InChiKey: IBDUIWKIDDWWQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-N-(2-aminoethyl)-6-phenylpyrimidine-2,4-diamine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 40.0h， 生成 4-N-[2-[(2-amino-6-phenylpyrimidin-4-yl)amino]ethyl]-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
• 作为产物：
  描述：

  tert-butyl N-[2-[(2-amino-6-chloropyrimidin-4-yl)amino]ethyl]carbamate 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 32.0h， 生成 4-N-(2-aminoethyl)-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

• MTH1 INHIBITORS FOR TREATMENT OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS
  申请人：THOMAS HELLEDAYS STIFTELSE FOR MEDICINSK FORSKNING

  公开号：US20170196873A1

  公开（公告）日：2017-07-13

  A compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of autoimmune diseases and inflammatory conditions.
• MTH1 INHIBITORS FOR TREATMENT OF CANCER
  申请人：THOMAS HELLEDAYS STIFTELSE FOR MEDICINSK FORSKNING

  公开号：US20170197976A1

  公开（公告）日：2017-07-13

  A compound of formula I, (I) or a pharmaceutically-acceptable salt thereof. The compound is useful in the treatment of cancer.