2-[2-氨基-6-(4-甲基哌嗪-1-基)嘧啶-4-基]苯甲腈 | 1028328-01-9

• 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: 2-[2-氨基-6-(4-甲基哌嗪-1-基)嘧啶-4-基]苯甲腈
• 英文名称: 2-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile
• CAS: 1028328-01-9
• 化学式: C₁₆H₁₈N₆
• 分子量: 294.359
• InChiKey: DPVCCUZXFVMHGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-6-(4-甲基哌嗪-1-基)嘧啶-2-胺 、 2-氰基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 16.0h， 以12%的产率得到2-[2-氨基-6-(4-甲基哌嗪-1-基)嘧啶-4-基]苯甲腈
  参考文献：
  名称：

  Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands

  摘要：

  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.

  DOI：

  10.1021/jm8005959

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。
• US7985745B2
  申请人：——

  公开号：US7985745B2

  公开（公告）日：2011-07-26
• 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.