2-[4-(3-chloropropoxy)phenyl]-4,4,5,5,-tetramethyl[1,3,2]dioxaborolane | 889865-32-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[4-(3-chloropropoxy)phenyl]-4,4,5,5,-tetramethyl[1,3,2]dioxaborolane
• 英文别名: 2-[4-(3-chloro-propoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane；4,4,5,5-tetramethyl-2-(4-(3-chloropropoxy)phenyl)-1,3,2-dioxaborolane；2-[4-(3-Chloropropoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• CAS: 889865-32-1
• 化学式: C₁₅H₂₂BClO₃
• 分子量: 296.602
• InChiKey: OPQUKGKJTWQAKY-UHFFFAOYSA-N

物化性质

• 沸点：
  400.4±25.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(3-chloropropoxy)phenyl]-4,4,5,5,-tetramethyl[1,3,2]dioxaborolane 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 、 sodium iodide 、 lithium chloride 作用下， 以 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 42.0h， 生成 1-methyl-4-{4-[3-((2R)-2-methyl-1-pyrrolidinyl)propoxy]phenyl}-2(1H)-pyridone
  参考文献：
  名称：

  Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists

  摘要：

  6-{4-[3-(R)-2-Methylpyrrolidin-1-yl) propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H3R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H3R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H3R affinity. N-Methyl 9b showed excellent H3R affinity, acceptable pharmacokinetics and pharmaceutical properties. In vivo evaluation of 9b showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.091
• 作为产物：
  描述：

  1-溴-3-氯丙烷 、 4-羟基苯硼酸频哪醇酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 2-[4-(3-chloropropoxy)phenyl]-4,4,5,5,-tetramethyl[1,3,2]dioxaborolane
  参考文献：
  名称：

  发现和表征6- {4- [3-（R）-2-甲基吡咯烷基-1-基）丙氧基]苯基} -2 H-哒嗪-3-酮（CEP-26401，依达比松）：有效的选择性组胺H 3受体反向激动剂

  摘要：

  新型哒嗪-3-一组胺H 3受体（H 3 R）拮抗剂/反向激动剂的优化确定了6- {4- [3-（R）-2-甲基吡咯烷-1-基）丙氧基]苯基}- 2 H-哒嗪-3-酮（8a，CEP-26401； irdabisant）作为潜在候选药物可用于治疗注意力和认知障碍。8a对人（K i = 2.0 nM）和大鼠（K i = 7.2 nM）H 3 Rs具有高亲和力，在hH 1 R，hH 2 R和hH 4上的选择性大于1000倍R组胺受体亚型，在418 G蛋白偶联受体，离子通道，转运蛋白和酶的体外实验中。图8a证明了CNS药物在水溶性，渗透性和亲脂性方面的理想药物特性，并且与人血浆蛋白的结合性低。它微弱地抑制了重组细胞色素P450亚型和与人类醚相关的基因。大鼠，小鼠，狗和人肝微粒体中的8a代谢极少，并且具有良好的种间药代动力学特性。图8a在大鼠中剂量依赖性地抑制了H 3 R激动剂诱导的成遗传（ED 50＝

  DOI：

  10.1021/jm200401v

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，其制备方法和药物组合物。
• 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。
• 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。