4-(4-氯苯基)-6-(4-甲基哌嗪-1-基)嘧啶-2-基胺 | 1028327-73-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-(4-氯苯基)-6-(4-甲基哌嗪-1-基)嘧啶-2-基胺
• 英文名称: 4-(4-chlorophenyl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine
• 英文别名: 4-(4-Chlorophenyl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine
• CAS: 1028327-73-2
• 化学式: C₁₅H₁₈ClN₅
• 分子量: 303.794
• InChiKey: YYUPHZVTHXGIJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 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 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 4-(4-氯苯基)-6-(4-甲基哌嗪-1-基)嘧啶-2-基胺
  参考文献：
  名称：

  Mapping histamine H₄receptor–ligand binding modes

  摘要：

  G蛋白偶联受体（GPCRs）中配体结合模式的计算预测仍然是一项具有挑战性的任务。在广泛的分子动力学（MD）模拟研究中系统考虑不同的蛋白建模模板、配体结合姿态和配体质子化状态，使得能够预测组胺H₄受体中特定配体突变效应，该受体在炎症中起关键作用。

  DOI：

  10.1039/c2md20212c

文献信息

• Method for Pain Treatment
  申请人：Cowart Marlon D.

  公开号：US20080194538A1

  公开（公告）日：2008-08-14

  This invention discloses a method of treating pain by administering histamine H 4 receptor ligands and compositions comprising the same.

  这项发明揭示了一种通过给予组织胺H4受体配体和包含相同的组合物来治疗疼痛的方法。
• Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands
  作者：Robert J. Altenbach、Ronald M. Adair、Brian M. Bettencourt、Lawrence A. Black、Shannon R. Fix-Stenzel、Sujatha M. Gopalakrishnan、Gin C. Hsieh、Huaqing Liu、Kennan C. Marsh、Michael J. McPherson、Ivan Milicic、Thomas R. Miller、Timothy A. Vortherms、Usha Warrior、Jill M. Wetter、Neil Wishart、David G. Witte、Prisca Honore、Timothy A. Esbenshade、Arthur A. Hancock、Jorge D. Brioni、Marlon D. Cowart

  DOI：10.1021/jm8005959

  日期：2008.10.23

  A series of 2-aminopyrimidines was synthesized as ligands of the histamine H-4 receptor (H4R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3,4-tert-butyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine. We further studied this compound by systematically modifying the core pyrimidine moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions 5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from this optimization, especially in analogs in which the 6-tert-butyl was replaced with aromatic and secondary amine moieties. The highlight of the optimization campaign was compound 4, 4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory agent in an animal model and had antinociceptive activity in a pain model, which supports the potential of H4R antagonists in pain.
• US7985745B2
  申请人：——

  公开号：US7985745B2

  公开（公告）日：2011-07-26
• Mapping histamine H₄receptor–ligand binding modes
  作者：Sabine Schultes、Saskia Nijmeijer、Harald Engelhardt、Albert J. Kooistra、Henry F. Vischer、Iwan J. P. de Esch、Eric E. J. Haaksma、Rob Leurs、Chris de Graaf

  DOI：10.1039/c2md20212c

  日期：——

  Computational prediction of ligand binding modes in G protein-coupled receptors (GPCRs) remains a challenging task. Systematic consideration of different protein modelling templates, ligand binding poses, and ligand protonation states in extensive molecular dynamics (MD) simulation studies enabled the prediction of ligand-specific mutation effects in the histamine H₄receptor, a key player in inflammation.

  G蛋白偶联受体（GPCRs）中配体结合模式的计算预测仍然是一项具有挑战性的任务。在广泛的分子动力学（MD）模拟研究中系统考虑不同的蛋白建模模板、配体结合姿态和配体质子化状态，使得能够预测组胺H₄受体中特定配体突变效应，该受体在炎症中起关键作用。