4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-6-chloropyrimidine-2,4-diamine | 1204744-65-9

• 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-[(2-aminopyrimidin-4-yl)amino]ethyl]-6-chloropyrimidine-2,4-diamine
• 英文别名: N4-{2-[(2-aminopyrimidin-4-yl)amino]ethyl}-6-chloropyrimidine-2,4-diamine
• CAS: 1204744-65-9
• 化学式: C₁₀H₁₃ClN₈
• 分子量: 280.72
• InChiKey: YVDXLELWUSFYJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-6-chloropyrimidine-2,4-diamine 在 5%-palladium/activated carbon 、 palladium(II) hydroxide 、 三乙胺 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、400.01 kPa 条件下， 反应 3.0h， 以51%的产率得到4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]pyrimidine-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-aminopyrimidin-4-yl)amino]ethyl]carbamate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 水 为溶剂， 反应 88.0h， 生成 4-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-6-chloropyrimidine-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

• AMINO HETEROCYCLIC LINKED PYRIMIDINE DERIVATIVES
  申请人：Wakefield Brian D.

  公开号：US20100016344A1

  公开（公告）日：2010-01-21

  Macrocyclic benzofused pyrimidine compounds, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions and disorders using such compounds and compositions are described herein.

  本文描述了大环苯并嘧啶化合物、包含这种化合物的组合物、制备这种化合物的方法，以及利用这种化合物和组合物治疗和预防疾病、症状和障碍的方法。
• Amino heterocyclic linked pyrimidine derivatives
  申请人：Abbott Laboratories

  公开号：US08268846B2

  公开（公告）日：2012-09-18

  Macrocyclic benzofused pyrimidine compounds, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions and disorders using such compounds and compositions are described herein.

  本文描述了大环苯并嘧啶化合物、包含此类化合物的组合物、制备该化合物的方法，以及使用该化合物和组合物治疗和预防疾病、病况和障碍的方法。
• Bispyrimidines as Potent Histamine H₄ Receptor Ligands: Delineation of Structure–Activity Relationships and Detailed H₄ Receptor Binding Mode
  作者：Harald Engelhardt、Sabine Schultes、Chris de Graaf、Saskia Nijmeijer、Henry F. Vischer、Obbe P. Zuiderveld、Julia Dobler、Katharina Stachurski、Moriz Mayer、Heribert Arnhof、Dirk Scharn、Eric E. J. Haaksma、Iwan J. P. de Esch、Rob Leurs

  DOI：10.1021/jm301886t

  日期：2013.6.13

  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.