1-[4-(3-chloropropoxy)phenyl]propan-2-one | 120373-93-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[4-(3-chloropropoxy)phenyl]propan-2-one
• 英文别名: 4-(3-Chloropropoxy)phenylacetone
• CAS: 120373-93-5
• 化学式: C₁₂H₁₅ClO₂
• 分子量: 226.703
• InChiKey: VDVIFFAJCAPPAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[4-(3-chloropropoxy)phenyl]propan-2-one 在 盐酸 、 水 、 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 24.0h， 生成 6-methyl-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：

  4-羟基苯基丙酮 、 1-溴-3-氯丙烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以93%的产率得到1-[4-(3-chloropropoxy)phenyl]propan-2-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

文献信息

• Fluorescence polymerization immunoassay for amphetamine/methamphetamine
  申请人：Abbott Laboratories

  公开号：US04952336A1

  公开（公告）日：1990-08-28

  This disclosure relates to a method and reagents for determining amphetamine and methamphetamine in a biological fluid such as urine. In particular, this disclosure relates to a fluorescence polarization immunoassay procedure for determining the presence of amphetamine and methamphetamine in a single assay and to a novel class of tracer compounds employed as reagents in such procedures. The procedure described includes pretreatment of the biological sample to eliminate cross-reactants such as .beta.-hydroxyphenethylamine by preincubating the sample solely with an aqueous periodate solution having a pH from about 4.0 to about 7.5 without adjustment to an alkaline pH.

  本公开涉及一种用于测定生物液体（如尿液）中安非他命和甲基安非他命的方法和试剂。特别地，本公开涉及一种荧光偏振免疫测定程序，用于在单个测定中确定安非他命和甲基安非他命的存在，并涉及一种新型的示踪剂化合物，作为这些程序中的试剂。所述程序包括对生物样本的预处理，以消除交叉反应物，例如β-羟基苯乙胺，仅通过用pH约为4.0至约7.5的水期酸溶液对样本进行预孵育，而不调整为碱性pH。
• Fluorescence polarization immunoassay for amphetamine/methamphetamine
  申请人：Abbott Laboratories

  公开号：US04868132A1

  公开（公告）日：1989-09-19

  This disclosure relates to a method and reagents for determining amphetamine and methamphetamine in a biological fluid such as urine. In particular, this disclosure relates to a fluorescence polarization immunoassay procedure for determining the presence of amphetamine and methamphetamine in a single assay and to a novel class of tracer compounds employed as reagents in such procedures. The procedure described includes pretreatment of the biological sample to eliminate cross-reactants such as .beta.-hydroxyphenethylamine by preincubating the sample solely with an aqueous periodate solution having a pH from about 4.0 to about 7.5 without adjustment to an alkaline pH.

  本公开涉及一种用于测定生物液体（如尿液）中苯丙胺和甲基苯丙胺的方法和试剂。具体而言，本公开涉及一种荧光偏振免疫测定程序，用于确定单个测定中苯丙胺和甲基苯丙胺的存在，以及在这种程序中使用的新型示踪剂化合物的一类。所述程序包括对生物样品进行预处理，以消除交叉反应物，例如β-羟基苯乙胺，通过仅将样品与pH约为4.0至约7.5的水期酸溶液预孵育，而不需要调整为碱性pH。
• 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。