5-[4-(3-chloropropoxy)phenyl]-2,6-dimethyl-2H-pyridazin-3-one | 1005402-33-4

• 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-[4-(3-chloropropoxy)phenyl]-2,6-dimethyl-2H-pyridazin-3-one
• 英文别名: 5-[4-(3-chloro-propoxy)-phenyl]-2,6-dimethyl-2H-pyridazin-3-one；5-[4-(3-chloropropoxy)phenyl]-2,6-dimethylpyridazin-3-one
• CAS: 1005402-33-4
• 化学式: C₁₅H₁₇ClN₂O₂
• 分子量: 292.765
• InChiKey: QCVJMTJDOSWDAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-[4-(3-chloropropoxy)phenyl]-2,6-dimethyl-2H-pyridazin-3-one 在 盐酸 、 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 48.0h， 生成 2,6-dimethyl-5-[4-(3-piperidin-1-ylpropoxy)phenyl]-2H-pyridazin-3-one hydrochloride
  参考文献：
  名称：

  Optimization of 5-Pyridazin-3-one Phenoxypropylamines as Potent, Selective Histamine H₃ Receptor Antagonists with Potent Cognition Enhancing Activity

  摘要：

  Previous studies have shown that (5-{4-[3-(R)-2-methylpyrrolin-1-yl-propoxy]phenyl}-2H-pyridazin-3-one) 2 had high affinity for both the human (hH(3)R K-i = 2.8 nM) and rat H(3)Rs (rH(3)R K-i = 8.5 nM) but displayed low oral bioavailability in the rat. Optimization of the 5-pyridazin-3-one R-2 and R-6 positions to improve the pharmacokinetic properties over 2 led to the identification of 5-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2-pyridin-2-yl-2H-pyridazin-3-one 29. Compound 29 displayed high affinity for both human and rat H(3)Rs (hH3R K-i = 1.7 nM, rH(3)R K = 3.7 nM) with a greater than 1000-fold selectivity over the other histamine receptor subtypes and favorable pharmacokinetic properties across species (F = 78% rat, 92% dog, 96% monkey). It showed low binding to human plasma proteins, weakly inhibited cytochrome P450 isoforms, and displayed an excellent safety profile for a CNS-active compound. 29 displayed potent H3R antagonist activity in the brain in a rat dipsogenia model and demonstrated enhancement of cognitive function in a rat social recognition model at low doses. However, the development of compound 29 was discontinued because of genotoxicity.

  DOI：

  10.1021/jm201295j
• 作为产物：
  描述：

  对甲氧基苯基丙酮 在 水 、 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 5-[4-(3-chloropropoxy)phenyl]-2,6-dimethyl-2H-pyridazin-3-one
  参考文献：
  名称：

  Optimization of 5-Pyridazin-3-one Phenoxypropylamines as Potent, Selective Histamine H₃ Receptor Antagonists with Potent Cognition Enhancing Activity

  摘要：

  Previous studies have shown that (5-{4-[3-(R)-2-methylpyrrolin-1-yl-propoxy]phenyl}-2H-pyridazin-3-one) 2 had high affinity for both the human (hH(3)R K-i = 2.8 nM) and rat H(3)Rs (rH(3)R K-i = 8.5 nM) but displayed low oral bioavailability in the rat. Optimization of the 5-pyridazin-3-one R-2 and R-6 positions to improve the pharmacokinetic properties over 2 led to the identification of 5-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2-pyridin-2-yl-2H-pyridazin-3-one 29. Compound 29 displayed high affinity for both human and rat H(3)Rs (hH3R K-i = 1.7 nM, rH(3)R K = 3.7 nM) with a greater than 1000-fold selectivity over the other histamine receptor subtypes and favorable pharmacokinetic properties across species (F = 78% rat, 92% dog, 96% monkey). It showed low binding to human plasma proteins, weakly inhibited cytochrome P450 isoforms, and displayed an excellent safety profile for a CNS-active compound. 29 displayed potent H3R antagonist activity in the brain in a rat dipsogenia model and demonstrated enhancement of cognitive function in a rat social recognition model at low doses. However, the development of compound 29 was discontinued because of genotoxicity.

  DOI：

  10.1021/jm201295j

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。
• Furanone Compounds and Methods of Making and Using The Same
  申请人：Sun Lihong

  公开号：US20100105714A1

  公开（公告）日：2010-04-29

  The invention features compounds of the general Formula (I): (formula should be inserted here) Compounds of Formula (I) possess unexpectedly high affinity for Alk5 and/or Alk4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders.

  本发明涉及一般式（I）的化合物：（应在此插入公式）。式（I）的化合物具有意外的高亲和力，可用作Alk5和/或Alk4的拮抗剂，以预防和/或治疗许多疾病，包括纤维化疾病。
• 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：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。
• Aryl pyridazinone derivatives and their use as H3 receptor ligands
  申请人：Bacon Edward R.

  公开号：US08586588B2

  公开（公告）日：2013-11-19

  The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds and/or their pharmaceutically acceptable salts 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，这些化合物及/或其药学上可接受的盐可能在治疗与组胺H3受体活性相关的疾病或疾病状态方面有效，包括神经退行性疾病、睡眠/觉醒障碍、注意力缺陷多动症和认知/认知障碍等。