tert-butyl N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]carbamate | 1204744-52-4

• 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: tert-butyl N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]carbamate
• 英文别名: tert-butyl 2-(2-aminopyrimidin-4-ylamino)ethylcarbamate
• CAS: 1204744-52-4
• 化学式: C₁₁H₁₉N₅O₂
• 分子量: 253.304
• InChiKey: WWJSXWBXNHDUFO-UHFFFAOYSA-N

物化性质

• 密度：
  1.211±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 112.0h， 生成 6-N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]-4-N-(2-methylpropyl)pyrimidine-2,4,6-triamine
  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：

  N-叔丁氧羰基-1,2-乙二胺 在 氨 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 20.0~150.0 ℃ 、700.01 kPa 条件下， 反应 96.0h， 生成 tert-butyl N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]carbamate
  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

• Synthesis and Functional Characterization of Imbutamine Analogs as Histamine H₃and H₄Receptor Ligands
  作者：Roland Geyer、Melanie Kaske、Paul Baumeister、Armin Buschauer

  DOI：10.1002/ardp.201300316

  日期：2014.2

  EC50 = 59 nM, α = 0.8) was equipotent with imbutamine at the hH4R, but revealed about 16‐fold selectivity for the hH4R compared to the hH3R (EC50 980 nM, α = 0.36), whereas imbutamine preferred the hH3R. The functional activities were in agreement with radioligand binding data. The results support the hypothesis that, by analogy with histamine, methyl substitution in histamine homologs offers a way to shift the

  Imbutamine (4-(1H-imidazol-4-yl)butanamine) 是一种有效的组胺 H3 (H3R) 和 H4 受体 (H4R) 激动剂（EC50 值分别为 3 和 66 nM）。为了提高对 H4R 的选择性，伊布巴明中的咪唑环被甲基取代或被各种不同取代的杂环（1,2,3-三唑、1,2,4-三唑、吡啶、嘧啶）取代，作为潜在的生物电子等排体。使用表达相应人组胺受体亚型的 Sf9 昆虫细胞膜对 [35S]GTPγS 结合测定进行的研究表明，大多数合成的杂芳基烷基胺对两种受体仅具有非常微弱的活性。相比之下，在 4-咪唑基环上引入取代基对 H4R 选择性最有效。这适用于第 2 位的甲基取代，尤其是第 5 位的甲基取代。 5-甲基丁二胺 (H4R: EC50 = 59 nM, α = 0.8) 在 hH4R 上与伊姆布塔明等效，但与 hH3R 相比，hH4R 的选择性大约是 hH3R
• 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。
• 4-SUBSTITUTED-2-AMINO-PYRIMIDINE DERIVATIVES
  申请人：Black Lawrence A.

  公开号：US20100331294A1

  公开（公告）日：2010-12-30

  Compounds of the formula wherein R 1 and R 2 are as disclosed herein, are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor full or partial agonists. Also disclosed are pharmaceutical compositions, methods for using such compounds and compositions, and processes for preparing the compounds.

  其中R1和R2如本文所披露的那样的化合物，在治疗通过组胺-3受体的全或部分激动剂预防或缓解的病症或疾病中是有用的。还披露了药物组合物、使用这类化合物和组合物的方法，以及制备这类化合物的过程。
• 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。
• 4-substituted-2-amino-pyrimidine derivatives
  申请人：Black Lawrence A.

  公开号：US08796297B2

  公开（公告）日：2014-08-05

  Compounds of the formula wherein R1 and R2 are as disclosed herein, are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor full or partial agonists. Also disclosed are pharmaceutical compositions, methods for using such compounds and compositions, and processes for preparing the compounds.

  式中R1和R2如本文所述，的化合物在治疗由组胺3受体全或部分激动剂预防或改善的疾病或症状中是有用的。还披露了制药组合物、使用这种化合物和组合物的方法以及制备这种化合物的过程。