5,8-Dichloropyrido[2,3-b][1,5]benzoxazepine | 1026795-53-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5,8-Dichloropyrido[2,3-b][1,5]benzoxazepine
• CAS: 1026795-53-8
• 化学式: C₁₂H₆Cl₂N₂O
• 分子量: 265.098
• InChiKey: ZZBDUCWEZMDRSL-UHFFFAOYSA-N

物化性质

• 沸点：
  423.3±55.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 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：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[2-(2-羟基乙氧基)乙基]哌嗪 、 5,8-Dichloropyrido[2,3-b][1,5]benzoxazepine 以 甲苯 为溶剂， 生成 5-[4-(2-hydroxyethoxyethyl)piperazin-1-yl]-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
• 作为产物：
  描述：

  3-溴-2-氯吡啶 在 palladium diacetate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 5,8-Dichloropyrido[2,3-b][1,5]benzoxazepine
  参考文献：
  名称：

  使用八羰基二钴作为有效的 CO 源一锅法合成取代的二苯并氧杂氮杂酮和吡啶并苯并氧杂氮杂酮

  摘要：

  摘要 使用八羰基二钴 (Co2(CO)8) 作为有效的羰基金属源，从市售的芳基/杂芳基卤化物和氨基苯酚合成取代的二苯并氧杂氮杂酮和吡啶并苯并氧杂氮杂酮的简便一锅法已被证明。该方法通过芳基/杂芳基卤化物与氨基苯酚通过酰胺化和分子内环化的顺序偶联进行，得到二苯并恶氮杂酮/吡啶并苯并恶氮杂酮。图形概要

  DOI：

  10.1080/00397911.2019.1695277

文献信息

• Liegeois; Rogister; Bruhwyler, Journal of Medicinal Chemistry, 1994, vol. 37, # 4, p. 519 - 525
  作者：Liegeois、Rogister、Bruhwyler、Damas、Thuy Phuong Nguyen、Inarejos、Chleide、Mercier、Delarge

  DOI：——

  日期：——
• SAR analysis of novel non-peptidic NPBWR1 (GPR7) antagonists
  作者：Miguel Guerrero、Mariangela Urbano、Marie-Therese Schaeffer、Steven Brown、Hugh Rosen、Edward Roberts

  DOI：10.1016/j.bmcl.2012.12.030

  日期：2013.2

  In this Letter we report on the advances in our NPBWR1 antagonist program aimed at optimizing the 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one lead molecule previously obtained from a high-throughput screening (HTS)-derived hit. Synthesis and structure-activity relationships (SAR) studies around the 3,5-dimethylphenyl and 4-methoxyphenyl regions resulted in the identification of a novel series of non-peptidic submicromolar NPBWR1 antagonists based on a 5-chloro-4-(4-alkoxyphenoxy)-2-(benzyl)pyridazin-3(2H)-one chemotype. Amongst them, 5-chloro-2-(9H-fluoren-9-yl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one 9h (CYM50769) inhibited NPW activation of NPBWR1 with a submicromolar IC50, and displayed high selectivity against a broad array of off-targets with pharmaceutical relevance. Our medicinal chemistry study provides innovative non-peptidic selective NPBWR1 antagonists that may enable to clarify the biological role and therapeutic utility of the target receptor in the regulation of feeding behavior, pain, stress, and neuroendocrine function. (c) 2012 Elsevier Ltd. All rights reserved.
• One-pot synthesis of substituted dibenzoxazepinones and pyridobenzoxazepinones using octacarbonyldicobalt as an effective CO source
  作者：Kavitha Anchan、Poongavanam Baburajan、Nagaswarupa H. Puttappa、Sujit Kumar Sarkar

  DOI：10.1080/00397911.2019.1695277

  日期：2020.2.1

  Abstract A facile one-pot protocol for the synthesis of substituted dibenzoxazepinones and pyridobenzoxazepinones from commercially available aryl/heteroaryl halides and amino phenols using octacarbonyldicobalt (Co2(CO)8) as an effective metal carbonyl source has been demonstrated. This method proceeds via the sequential coupling of aryl/heteroaryl halides with aminophenol by amidation and intramolecular

  摘要 使用八羰基二钴 (Co2(CO)8) 作为有效的羰基金属源，从市售的芳基/杂芳基卤化物和氨基苯酚合成取代的二苯并氧杂氮杂酮和吡啶并苯并氧杂氮杂酮的简便一锅法已被证明。该方法通过芳基/杂芳基卤化物与氨基苯酚通过酰胺化和分子内环化的顺序偶联进行，得到二苯并恶氮杂酮/吡啶并苯并恶氮杂酮。图形概要
• 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.