8-chloro-4-fluoro-dibenzo[b,f][1,4]oxazepin-11(10H)-one | 908336-79-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-chloro-4-fluoro-dibenzo[b,f][1,4]oxazepin-11(10H)-one
• 英文别名: 8-chloro-4-fluorodibenzo[b,f][1,4]oxazepin-11(10H)-one；3-chloro-10-fluoro-5H-benzo[b][1,4]benzoxazepin-6-one
• CAS: 908336-79-8
• 化学式: C₁₃H₇ClFNO₂
• 分子量: 263.655
• InChiKey: QUDRQGUYSNFMSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-chloro-4-fluoro-dibenzo[b,f][1,4]oxazepin-11(10H)-one 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 8-chloro-4-fluoro-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
• 作为产物：
  描述：

  2,3-二氟苯甲酸 在 sodium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 8-chloro-4-fluoro-dibenzo[b,f][1,4]oxazepin-11(10H)-one
  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

• A highly-efficient palladium-catalyzed aminocarbonylation/S_NAr approach to dibenzoxazepinones
  作者：Chaoren Shen、Helfried Neumann、Xiao-Feng Wu

  DOI：10.1039/c5gc00427f

  日期：——

  A practical protocol for the synthesis of dibenzo[b,e][1,4]oxazepin-11(5H)-ones has been developed. By virtue of Pd-catalyzed aminocarbonylation and aromatic nucleophilic substitution, 61 examples of the desired dibenzoxazepinones were obtained in moderate to excellent isolated yields (54-92%).

  已经开发了一种实用的合成二苯并[b，e] [1,4]草酰pin11（5H）-ones的协议。借助于Pd催化的氨基羰基化和芳族亲核取代，以中等至优异的分离产率（54-92％）获得了61个所需的二苯并恶嗪酮类实例。
• 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.