5-(2-(piperidin-1-yl)ethylamino)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine | 1358939-83-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(2-(piperidin-1-yl)ethylamino)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine
• 英文别名: 8-chloro-N-(2-piperidin-1-ylethyl)-6H-pyrido[2,3-b][1,5]benzoxazepin-5-imine
• CAS: 1358939-83-9
• 化学式: C₁₉H₂₁ClN₄O
• 分子量: 356.855
• InChiKey: JQWKOVNMSGDRRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-氨乙基)哌啶 、 8-chlorobenzo[b]pyrido[3,2-f ][1,4]oxazepin-5(6H)-one 在 四氯化钛 、 苯甲醚 作用下， 以 甲苯 为溶剂， 生成 5-(2-(piperidin-1-yl)ethylamino)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine
  参考文献：
  名称：

  New Pyridobenzoxazepine Derivatives Derived from 5-(4-Methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13): Chemical Synthesis and Pharmacological Evaluation

  摘要：

  A series of new pyridobenzoxazepine derivatives with various heterocyclic amine side chains were synthesized to explore two main parameters related to the distal basic nitrogen. These compounds were tested for their affinity for dopamine D-2L and D-4, serotonin 5-HT1A and 5-HT2A, and adrenergic alpha(2A) receptors in comparison with 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,34][1,5]benzoxazepine, JL13 (1), and other diarylazepine derivatives. In terms of multireceptor target strategy, 2 and 5 present the most promising in vitro binding profile. Bulky, polar, and more flexible side chains are not favorable in this context. Compounds 2 and 5 were tested in adult rats to evaluate their long-term effects on dopamine and serotonin receptors density in different brain areas. Similar to 1 and other second-generation antipsychotic drugs, repeated treatment with 2 significantly increased D-1 and D-4 receptors in nucleus accumbens and caudate putamen and D-2 receptors in medial prefrontal cortex and hippocampus, while 5 significantly increased D-2 and D-4 receptors in nucleus accumbens. In addition, 2 increased 5-HT1A and decreased 5-HT2A receptors in cerebral cortex. In contrast, 5 did not alter levels of any 5-HT receptor subtype in any brain region examined. These results encourage further development of 2 as a novel second-generation antipsychotic agent.

  DOI：

  10.1021/jm2013419

文献信息

• New Pyridobenzoxazepine Derivatives Derived from 5-(4-Methylpiperazin-1-yl)-8-chloro-pyrido[2,3-<i>b</i>][1,5]benzoxazepine (JL13): Chemical Synthesis and Pharmacological Evaluation
  作者：Jean-François Liégeois、Marine Deville、Sébastien Dilly、Cédric Lamy、Floriane Mangin、Mélissa Résimont、Frank I. Tarazi

  DOI：10.1021/jm2013419

  日期：2012.2.23

  A series of new pyridobenzoxazepine derivatives with various heterocyclic amine side chains were synthesized to explore two main parameters related to the distal basic nitrogen. These compounds were tested for their affinity for dopamine D-2L and D-4, serotonin 5-HT1A and 5-HT2A, and adrenergic alpha(2A) receptors in comparison with 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,34][1,5]benzoxazepine, JL13 (1), and other diarylazepine derivatives. In terms of multireceptor target strategy, 2 and 5 present the most promising in vitro binding profile. Bulky, polar, and more flexible side chains are not favorable in this context. Compounds 2 and 5 were tested in adult rats to evaluate their long-term effects on dopamine and serotonin receptors density in different brain areas. Similar to 1 and other second-generation antipsychotic drugs, repeated treatment with 2 significantly increased D-1 and D-4 receptors in nucleus accumbens and caudate putamen and D-2 receptors in medial prefrontal cortex and hippocampus, while 5 significantly increased D-2 and D-4 receptors in nucleus accumbens. In addition, 2 increased 5-HT1A and decreased 5-HT2A receptors in cerebral cortex. In contrast, 5 did not alter levels of any 5-HT receptor subtype in any brain region examined. These results encourage further development of 2 as a novel second-generation antipsychotic agent.