1-[3-(1H-imidazol-4-ylmethyl)phenyl]-3,3-dimethylbutan-1-one | 1029690-36-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[3-(1H-imidazol-4-ylmethyl)phenyl]-3,3-dimethylbutan-1-one
• 英文别名: 1-[3-(1H-imidazol-5-ylmethyl)phenyl]-3,3-dimethylbutan-1-one
• CAS: 1029690-36-5
• 化学式: C₁₆H₂₀N₂O
• 分子量: 256.348
• InChiKey: SHQNNJIERWMYHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-[3-(3,3-dimethylbut-1-ynyl)benzyl]-1H-imidazole 在 水 、 三氟乙酸 作用下， 反应 4.0h， 生成 1-[3-(1H-imidazol-4-ylmethyl)phenyl]-3,3-dimethylbutan-1-one
  参考文献：
  名称：

  4-Benzyl-1H-imidazoles with Oxazoline Termini as Histamine H₃ Receptor Agonists

  摘要：

  Research on the therapeutic applications of the histamine H-3 receptor (H3R) has traditionally focused on antagonists/inverse agonists. In contrast, H3R acyonists have received less attention despite their potential use in several disease areas. The lower availability of H3R agonists not only hampers their full therapeutic exploration, it also prevents an unequivocal understanding of the structural requirements for H3R activation. In the light of these important issues, we present our findings on 4-benzyl-1H-imidazole-based H3R agonists. Starting from two high throughput screen hits (10 and 11), the benzyl side chain was altered with lipophilic groups using combinatorial and classical chemical approaches (compounds 12-31). Alkyne- or oxazolino-substituents gave excellent affinities and agonist activities up to the single digit nM range. Our findings further substantiate the growing notion that basic ligand sidechains are not necessary for H3R activation and reveal the oxazolino group as a hitherto unexplored functional group in H3R research.

  DOI：

  10.1021/jm7014149

文献信息

• 4-Benzyl-1<i>H</i>-imidazoles with Oxazoline Termini as Histamine H₃ Receptor Agonists
  作者：Maikel Wijtmans、Sylvain Celanire、Erwin Snip、Michel R. Gillard、Edith Gelens、Philippe P. Collart、Bastiaan J. Venhuis、Bernard Christophe、Saskia Hulscher、Henk van der Goot、Florence Lebon、Henk Timmerman、Remko A. Bakker、Bénédicte I. L. F. Lallemand、Rob Leurs、Patrice E. Talaga、Iwan J. P. de Esch

  DOI：10.1021/jm7014149

  日期：2008.5.1

  Research on the therapeutic applications of the histamine H-3 receptor (H3R) has traditionally focused on antagonists/inverse agonists. In contrast, H3R acyonists have received less attention despite their potential use in several disease areas. The lower availability of H3R agonists not only hampers their full therapeutic exploration, it also prevents an unequivocal understanding of the structural requirements for H3R activation. In the light of these important issues, we present our findings on 4-benzyl-1H-imidazole-based H3R agonists. Starting from two high throughput screen hits (10 and 11), the benzyl side chain was altered with lipophilic groups using combinatorial and classical chemical approaches (compounds 12-31). Alkyne- or oxazolino-substituents gave excellent affinities and agonist activities up to the single digit nM range. Our findings further substantiate the growing notion that basic ligand sidechains are not necessary for H3R activation and reveal the oxazolino group as a hitherto unexplored functional group in H3R research.