5-methoxy-2-methoxymethyl-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one | 1005401-18-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-methoxy-2-methoxymethyl-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one
• 英文别名: 5-Methoxy-2-methoxymethyl-4-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2H-pyridazin-3-one；5-methoxy-2-(methoxymethyl)-4-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one
• CAS: 1005401-18-2
• 化学式: C₂₁H₂₉N₃O₄
• 分子量: 387.479
• InChiKey: SOFLHSZGYGTBLR-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-methoxymethyl-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 72.0h， 以37%的产率得到5-methoxy-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one
  参考文献：
  名称：

  Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists

  摘要：

  A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H3R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H3R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.028
• 作为产物：
  描述：

  3-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propyl methanesulfonate 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 22.0h， 生成 5-methoxy-2-methoxymethyl-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one
  参考文献：
  名称：

  Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists

  摘要：

  A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H3R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H3R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.028

文献信息

• Pyridizinone derivatives
  申请人：Hudkins L. Robert

  公开号：US20080027041A1

  公开（公告）日：2008-01-31

  The present invention provides compounds of formula (I*): their use as H 3 inhibitors, processes for their preparation, and pharmaceutical compositions thereof.

  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。
• 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。
• PROCESSES FOR PREPARING (R)-2-METHYLPYRROLIDINE AND (S)-2-METHYLPYRROLIDINE AND TARTRATE SALTS THEREOF
  申请人：Christie Michael

  公开号：US20100121055A1

  公开（公告）日：2010-05-13

  The present invention provides a short, safe, inexpensive, commercially scalable process for preparing (R)- or (S)-2-methylpyrrolidine from 2-methylpyrroline, which does not require the isolation of synthetic intermediates.

  本发明提供了一种从2-甲基吡咯烷制备(R)-或(S)-2-甲基吡咯烷的简短、安全、廉价、商业可扩展的过程，不需要分离合成中间体。
• 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。