4,7-dichloro-11-(4-methylpiperazin-1-yl)-dibenzo[b,f][1,4]oxazepine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4,7-dichloro-11-(4-methylpiperazin-1-yl)-dibenzo[b,f][1,4]oxazepine
• 英文别名: 2,10-Dichloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine
• 化学式: C₁₈H₁₇Cl₂N₃O
• 分子量: 362.258
• InChiKey: SFRCYIYJFYOGHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  28.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,3-二氯苯甲酸 在 sodium hydroxide 、 氯化亚砜 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 9.0h， 生成 4,7-dichloro-11-(4-methylpiperazin-1-yl)-dibenzo[b,f][1,4]oxazepine
  参考文献：
  名称：

  Characterization of the Histamine H₄ Receptor Binding Site. Part 1. Synthesis and Pharmacological Evaluation of Dibenzodiazepine Derivatives

  摘要：

  A series of dibenzodiazepine derivatives was synthesized to probe the binding site of the recently discovered histamine H-4 receptor (H4R). Optimization of the lead structure clozapine (2) resulted in (E)-7-chloro-11-(4-methylpiperazin-l-yl) dibenzo[b, f][1,4] oxazepine (7j), a potent H4R agonist (H4R, pK(i) = 7.6). Pharmacological data suggests that the series of nonimidazole compounds can be used to describe the orthosteric binding site of the H4R because both 2 and 7j displace [H-3] histamine in a competitive manner. Furthermore, it is demonstrated that the effects of 7j are competitively antagonized by the selective H4R antagonist JNJ 7777120 (1), indicating considerable overlap of their binding sites. On the basis of the derived structure-activity relationships and additional pharmacological results, a pharmacophore model was constructed, which will be the premise for the design of novel H4R ligands.

  DOI：

  10.1021/jm051008s

文献信息

• Characterization of the Histamine H₄ Receptor Binding Site. Part 1. Synthesis and Pharmacological Evaluation of Dibenzodiazepine Derivatives
  作者：Rogier A. Smits、Herman D. Lim、Bart Stegink、Remko A. Bakker、Iwan J. P. de Esch、Rob Leurs

  DOI：10.1021/jm051008s

  日期：2006.7.1

  A series of dibenzodiazepine derivatives was synthesized to probe the binding site of the recently discovered histamine H-4 receptor (H4R). Optimization of the lead structure clozapine (2) resulted in (E)-7-chloro-11-(4-methylpiperazin-l-yl) dibenzo[b, f][1,4] oxazepine (7j), a potent H4R agonist (H4R, pK(i) = 7.6). Pharmacological data suggests that the series of nonimidazole compounds can be used to describe the orthosteric binding site of the H4R because both 2 and 7j displace [H-3] histamine in a competitive manner. Furthermore, it is demonstrated that the effects of 7j are competitively antagonized by the selective H4R antagonist JNJ 7777120 (1), indicating considerable overlap of their binding sites. On the basis of the derived structure-activity relationships and additional pharmacological results, a pharmacophore model was constructed, which will be the premise for the design of novel H4R ligands.