4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester | 1005402-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenoxy]piperidine-1-carboxylate
• CAS: 1005402-99-2
• 化学式: C₂₁H₂₉N₃O₄
• 分子量: 387.479
• InChiKey: OXBOUJDKVUVCPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以47%的产率得到5-methyl-6-[4-(piperidin-4-yloxy)-phenyl]-4,5-dihydro-2H-pyridazin-3-one
  参考文献：
  名称：

  Pyridizinone derivatives

  摘要：

  本发明提供了式(I*)的化合物：它们作为H3抑制剂的用途，其制备方法以及药物组合物。

  公开号：

  US20080027041A1
• 作为产物：
  描述：

  4-羟基苯丙酮 在 一水合肼 、 三苯基膦 、 lithium diisopropyl amide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 生成 4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  4-Phenoxypiperidine pyridazin-3-one histamine H3 receptor inverse agonists demonstrating potent and robust wake promoting activity

  摘要：

  Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.026

文献信息

• Pyridazinone Derivatives
  申请人：Bacon Edward R.

  公开号：US20110288075A1

  公开（公告）日：2011-11-24

  The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition/cognitive disorders.

  本发明涉及新型吡啶并咪唑酮衍生物，可介导酶活性。特别是，这些化合物可能在治疗与组胺H3受体活性相关的疾病或疾病状态方面具有有效性，包括神经退行性疾病、睡眠/清醒障碍、注意力缺陷多动障碍和认知/认知障碍等。
• Pyridazinone derivatives
  申请人：Cephalon, Inc.

  公开号：US08207168B2

  公开（公告）日：2012-06-26

  The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition disorders.

  本发明涉及介导酶活性的新型吡啶并咪唑酮衍生物。特别地，这些化合物可能对与组胺H3受体活性相关的疾病或疾病状态具有治疗作用，包括神经退行性疾病、睡眠/觉醒障碍、注意力缺陷多动障碍和认知障碍等。
• Pyridizinone derivatives and the use thereof as H3 inhibitors
  申请人：Cephalon, Inc.

  公开号：US08247414B2

  公开（公告）日：2012-08-21

  The present invention is directed to novel pyridizinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition.

  本发明涉及新型的吡啶酮衍生物，可以介导酶活性。特别地，这些化合物可能对与组胺H3受体活性相关的疾病或疾病状态具有治疗作用，例如神经退行性疾病、睡眠/觉醒障碍、注意力缺陷多动障碍和认知障碍。
• PYRIDAZINONE DERIVATIVES
  申请人：Bacon Edward R.

  公开号：US20140142088A1

  公开（公告）日：2014-05-22

  The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition.

  本发明涉及新型吡啶酮衍生物，可介导酶活性。特别地，这些化合物可能在治疗与组胺H3受体活性相关的疾病或疾病状态方面具有有效性，包括但不限于神经退行性疾病、睡眠/觉醒障碍、注意力缺陷多动障碍和认知方面。
• Methods of treating disorders mediated by histamine H3 receptors using pyridazinone derivatives
  申请人：Bacon Edward R.

  公开号：US08673916B2

  公开（公告）日：2014-03-18

  The present invention is directed to methods of treating disorders mediated by Histamine H3 receptors by administering novel pyridazinone derivatives. In particular, the pyridazinone compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition/cognitive disorders.

  本发明涉及通过给予新型吡啶并咪唑酮衍生物治疗由组胺H3受体介导的疾病的方法。特别地，吡啶并咪唑酮化合物可能对与组胺H3受体活性相关的疾病或疾病状态具有治疗作用，包括但不限于神经退行性疾病、睡眠/觉醒障碍、注意力缺陷多动障碍和认知/认知障碍。