2-[4-(3-chloropropoxy)phenyl]ethanol | 955359-96-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-[4-(3-chloropropoxy)phenyl]ethanol
• 英文别名: 2-{4-[(3-chloropropyl)oxy]phenyl}ethanol
• CAS: 955359-96-3
• 化学式: C₁₁H₁₅ClO₂
• 分子量: 214.692
• InChiKey: RRAQXQYAWFKRFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[4-(3-chloropropoxy)phenyl]ethanol 在 水 、 吗啡啉盐酸盐 、 potassium carbonate 、 戴斯-马丁氧化剂 、 溶剂黄146 、 sodium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 73.0h， 生成 5-{4-[3-((R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2-pyridin-2-yl-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
• 作为产物：
  描述：

  对羟基苯乙醇 、 1-溴-3-氯丙烷 在 potassium carbonate 作用下， 以 丁酮 为溶剂， 反应 18.0h， 生成 2-[4-(3-chloropropoxy)phenyl]ethanol
  参考文献：
  名称：

  基于喹啉的单配体人类H1和H3受体拮抗剂的发现。

  摘要：

  鉴定了一系列新颖的基于喹啉的有效人H1和H3二价组胺受体拮抗剂，适用于鼻内给药，可用于治疗变应性鼻炎相关的鼻充血。化合物18b的H1效力（临床金标准氮卓斯汀的pA2 8.8与9.7）和H3效力（氮卓斯汀的pKi 9.1vs 6.8）略低，选择性比α1A，α1B和hERG好，作用时间相似，因此18b的背甲好到我们之前的候选人，但具有更理想的配置。

  DOI：

  10.1016/j.bmcl.2016.11.022

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。
• [EN] QUINOLINE DERIVATIVES AND THEIR USES FOR RHINITIS AND URTICARIA<br/>[FR] DÉRIVÉS DE QUINOLINE ET APPLICATIONS ASSOCIÉES DANS LA RHINITE ET L'URTICAIRE
  申请人：GLAXO GROUP LTD

  公开号：WO2010094643A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及式(I)的化合物及其盐，其制备方法，含有它们的组合物，以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• COMPOUNDS
  申请人：GORE Martin Paul

  公开号：US20080039444A1

  公开（公告）日：2008-02-14

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

  本发明涉及式(I)化合物及其盐，其制备过程，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• 2-Substituted 4-Benzylphthalazinone Derivatives as Histamine H1 and H3 Antagonists
  申请人：Gore Paul Martin

  公开号：US20090105225A1

  公开（公告）日：2009-04-23

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

  本发明涉及公式(I)的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病，如过敏性鼻炎中的应用。
• 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。