6-chloro-N-methyl-2-(3,4,5-trimethylpiperazin-1-yl)quinazolin-4-amine | 1001065-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-chloro-N-methyl-2-(3,4,5-trimethylpiperazin-1-yl)quinazolin-4-amine
• CAS: 1001065-89-9
• 化学式: C₁₆H₂₂ClN₅
• 分子量: 319.837
• InChiKey: PAFOHHVKHIPRIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-dichloro-N-methylquinazolin-4-amine 、 1,2,6-trimethylpiperazine 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 0.17h， 生成 6-chloro-N-methyl-2-(3,4,5-trimethylpiperazin-1-yl)quinazolin-4-amine
  参考文献：
  名称：

  Discovery of Quinazolines as Histamine H₄ Receptor Inverse Agonists Using a Scaffold Hopping Approach

  摘要：

  From a series of small fragments that was designed to probe the histamine H-4 receptor (H4R), we previously described quinoxaline-containing fragments that were grown into high affinity H4R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H4R compounds. This approach led to the discovery of 6-chloi-o-N-(furan-3-yl)methyl)2-(4-methylpiperzin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H4R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine Hi receptor (H1R) and therefore represent a novel class of dual action H1R/H4R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quirlazolines are antagonists at the rat H4R and were found to possess anti-inflammatory properties in vivo in the rat.

  DOI：

  10.1021/jm800876b

文献信息

• Discovery of Quinazolines as Histamine H₄ Receptor Inverse Agonists Using a Scaffold Hopping Approach
  作者：Rogier A. Smits、Iwan J. P. de Esch、Obbe P. Zuiderveld、Joachim Broeker、Kamonchanok Sansuk、Elena Guaita、Gabriella Coruzzi、Maristella Adami、Eric Haaksma、Rob Leurs

  DOI：10.1021/jm800876b

  日期：2008.12.25

  From a series of small fragments that was designed to probe the histamine H-4 receptor (H4R), we previously described quinoxaline-containing fragments that were grown into high affinity H4R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H4R compounds. This approach led to the discovery of 6-chloi-o-N-(furan-3-yl)methyl)2-(4-methylpiperzin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H4R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine Hi receptor (H1R) and therefore represent a novel class of dual action H1R/H4R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quirlazolines are antagonists at the rat H4R and were found to possess anti-inflammatory properties in vivo in the rat.