6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]pyridine-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]pyridine-3-carboxamide
• 英文别名: 6-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)nicotiamide；GSK185071B；6-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-nicotinamide；6-[(3-Cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)oxy]pyridine-3-carboxamide
• 化学式: C₂₀H₂₃N₃O₂
• 分子量: 337.422
• InChiKey: GGCWRDSZXATELN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]pyridine-3-carboxamide 、 [11C]methyl iodide 在 四丁基氟化铵 作用下， 以 二甲基亚砜 为溶剂， 生成 [¹¹C]GSK-189254
  参考文献：
  名称：

  [EN] PIPERAZINE DERIVATIVE HAVING AFFINITY FOR THE HISTAMINE H3 RECEPTOR
  [FR] DÉRIVÉ DE PIPÉRAZINE PRÉSENTANT UNE AFFINITÉ POUR LE RÉCEPTEUR H3 DE L'HISTAMINE

  摘要：

  本发明涉及1-(1-甲基乙基)-4-{[4-(四氢-2H-吡喃-4-氧基)苯基]羰基}哌嗪（分子式）或其药学上可接受的盐，特别是其盐酸盐及其盐酸盐的结晶形式；制备该化合物或其盐的方法；含有它的组合物；以及其在治疗或预防神经系统或精神疾病，如认知障碍、疲劳或睡眠障碍等方面的用途，例如在哺乳动物中，如人类。该化合物或其盐对组织胺H3受体具有亲和力，并且是组织胺H3受体的拮抗剂和/或逆向激动剂。

  公开号：

  WO2009030716A1
• 作为产物：
  描述：

  3-甲氧基苯基乙酰氯 在 盐酸 、 硼烷四氢呋喃络合物 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 四丁基碘化铵 、 sodium hydride 、 溶剂黄146 、 三甲胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 、 mineral oil 为溶剂， 120.0 ℃ 、413.7 kPa 条件下， 反应 9.0h， 生成 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]pyridine-3-carboxamide
  参考文献：
  名称：

  A new facile synthetic route to [11C]GSK189254, a selective PET radioligand for imaging of CNS histamine H3 receptor

  摘要：

  GSK189254 and its corresponding precursor GSK185071B were synthesized from 3-methoxyphenylacetic acid with 6-chloropyridine-3-carbolic acid or 6-chloronicotinamide in 8 and 7 steps with either 6% or 7% and either 14% or 16% yield, respectively. [C-11]GSK189254 was prepared from GSK185071B with [C-11]CH3OTf through N-[C-11] methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 50-60% radiochemical yield based on [C-11]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/mu mol specific activity at EOB. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.076

文献信息

• [EN] PIPERAZINE DERIVATIVE HAVING AFFINITY FOR THE HISTAMINE H3 RECEPTOR<br/>[FR] DÉRIVÉ DE PIPÉRAZINE PRÉSENTANT UNE AFFINITÉ POUR LE RÉCEPTEUR H3 DE L'HISTAMINE
  申请人：GLAXO GROUP LTD

  公开号：WO2009030716A1

  公开（公告）日：2009-03-12

  The present invention relates to 1-(1-methylethyl)-4-[4-(tetrahydro-2H-pyran-4-yloxy)phenyl]carbonyl}piperazine (Formula) or a pharmaceutically acceptable salt thereof, in particular the hydrochloride salt thereof and crystalline forms of the hydrochloride salt; to processes for the preparation of the compound or its salt; to compositions containing it; and to its use in the treatment or prophylaxis of neurological or psychiatric diseases, such as cognitive impairment, fatigue or a sleep disorder, for example in a mammal such as a human. The compound or a salt thereof has affinity for and is an antagonist and/or inverse agonist of the histamine H3 receptor.

  本发明涉及1-(1-甲基乙基)-4-[4-(四氢-2H-吡喃-4-氧基)苯基]羰基}哌嗪（分子式）或其药学上可接受的盐，特别是其盐酸盐及其盐酸盐的结晶形式；制备该化合物或其盐的方法；含有它的组合物；以及其在治疗或预防神经系统或精神疾病，如认知障碍、疲劳或睡眠障碍等方面的用途，例如在哺乳动物中，如人类。该化合物或其盐对组织胺H3受体具有亲和力，并且是组织胺H3受体的拮抗剂和/或逆向激动剂。
• Benzo d!azepine derivatives for the treatment of neurological disorders
  申请人：Bamford James Mark

  公开号：US20060040918A1

  公开（公告）日：2006-02-23

  The present invention relates to benzazepine derivatives of formula (I) wherein: R 1 represents —C 3-7 cycloalkyl optionally substituted by C 1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

  本发明涉及式（I）的苯并唑啉衍生物，其中：R1代表- C3-7 环烷基，可选择性地被C1-3烷基取代; 具有药理活性，其制备过程，含有它们的组合物以及它们在治疗神经和精神障碍中的用途。
• BENZAZEPINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
  申请人：BAMFORD Mark James

  公开号：US20090105226A1

  公开（公告）日：2009-04-23

  The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

  本发明涉及具有药理活性的新型苯并氮杂环衍生物，其制备过程，含有它们的组合物以及它们在治疗神经系统和精神障碍中的应用。
• Piperazine Derivative Having Affinity for the Histamine H3 Receptor
  申请人：Best Desmond John

  公开号：US20100204242A1

  公开（公告）日：2010-08-12

  The present invention relates to 1-(1-methylethyl)-4-[4-(tetrahydro-2H-pyran-4-yloxy)phenyl]carbonyl}piperazine or a pharmaceutically acceptable salt thereof, in particular the hydrochloride salt thereof and crystalline forms of the hydrochloride salt; to processes for the preparation of the compound or its salt; to compositions containing it; and to its use in the treatment or prophylaxis of neurological or psychiatric diseases, such as cognitive impairment, fatigue or a sleep disorder, for example in a mammal such as a human. The compound or a salt thereof has affinity for and is an antagonist and/or inverse agonist of the histamine H3 receptor.

  本发明涉及1-(1-甲基乙基)-4-[4-(四氢-2H-吡喃-4-氧基)苯基]甲酰基}哌嗪或其药学上可接受的盐，特别是其盐酸盐及其盐酸盐的晶体形式；制备该化合物或其盐的过程；含有该化合物的组合物；以及在哺乳动物，例如人类中治疗或预防神经系统或精神疾病，如认知障碍、疲劳或睡眠障碍等方面的用途。该化合物或其盐具有亲和力并且是组胺H3受体的拮抗剂和/或反向激动剂。
• Benzazepine Derivatives For The Treatment of Neurological Disorders
  申请人：Bamford Mark James

  公开号：US20100145040A1

  公开（公告）日：2010-06-10

  The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

  本发明涉及具有药理活性的新型苯并氮杂环衍生物，其制备过程，含有它们的组合物以及它们在治疗神经系统和精神障碍方面的应用。