4-adamantan-1-yl-2,6-dichloropyrimidine

• 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-adamantan-1-yl-2,6-dichloropyrimidine
• 英文别名: 4-(1-Adamantyl)-2,6-dichloropyrimidine
• 化学式: C₁₄H₁₆Cl₂N₂
• mdl: MFCD05863457
• 分子量: 283.2
• InChiKey: CAXXEYFKFHMUAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.714
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 4-adamantan-1-yl-2,6-dichloropyrimidine 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以73%的产率得到4-adamantan-1-yl-2-chloro-6-(4-methylpiperazin-1-yl)pyrimidine
  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
• 作为产物：
  描述：

  2,4,6-三氯嘧啶 、 1-金刚烷甲酸 在 ammonium persulfate 、 silver nitrate 作用下， 以 水 、 乙腈 为溶剂， 反应 2.2h， 以16%的产率得到4-adamantan-1-yl-2,6-dichloropyrimidine
  参考文献：
  名称：

  Kanomata, Nobuhiro; Igarashi, Mamoru; Tada, Masaru, Heterocycles, 1993, vol. 36, # 5, p. 1127 - 1138

  摘要：

  DOI：

文献信息

• 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.
• Kanomata, Nobuhiro; Igarashi, Mamoru; Tada, Masaru, Heterocycles, 1993, vol. 36, # 5, p. 1127 - 1138
  作者：Kanomata, Nobuhiro、Igarashi, Mamoru、Tada, Masaru

  DOI：——

  日期：——