N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide | 935840-31-6

• 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: N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide
• 英文别名: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutanecarboxamide
• CAS: 935840-31-6
• 化学式: C₁₈H₂₄F₂N₂O
• 分子量: 322.398
• InChiKey: SXMBKHYDZOCBMT-PPUGGXLSSA-N

物化性质

• 沸点：
  460.5±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  32.34
• 氢给体数：
  1.0
• 氢受体数：
  2.0

制备方法与用途

PF-03654746 是一种有效的选择性 H3 历史胺 H3 受体拮抗剂，具有较高的脑渗透性。它能够减少过敏原引起的鼻腔症状，并可能成为治疗过敏性鼻炎的新型策略。此外，PF-03654746 还能提高阿尔茨海默病患者的认知功能并改善疾病状况。

反应信息

• 作为反应物：
  描述：

  N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide 、 对甲苯磺酸 以 乙酸乙酯 为溶剂， 反应 1.33h， 生成 N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide,4-methylbenzenesulfonic acid
  参考文献：
  名称：

  TOLUENE SULFONIC ACID SALT OF A THERAPEUTIC COMPOUND AND PHARMACEUTICAL COMPOSITIONS THEREOF

  摘要：

  本发明涉及对氟醚脲基环丁烷羧酰胺的对甲苯磺酸盐（1）：其溶剂化合物（例如水合物）、其多型体、其药物组合物以及治疗抑郁症、情绪障碍、精神分裂症、焦虑症、认知障碍、阿尔茨海默病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、精神障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸道疾病、过敏、过敏引起的气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、胃肠道疾病、胃肠道高低蠕动和酸性分泌包括给予其治疗有效量的方法。

  公开号：

  US20080176925A1

文献信息

• HISTAMINE-3 RECEPTOR ANTAGONISTS
  申请人：Wager T. Travis

  公开号：US20080096955A1

  公开（公告）日：2008-04-24

  This invention is directed to a compound of formula I, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a process of preparation of a compound of formula I, a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit hyperactivity disorder (ADHD), psychotic disorders, cognitive disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above.

  本发明涉及一种式I的化合物，如本文所定义，或其药学上可接受的盐；包含式I化合物的制药组合物；制备式I化合物的方法；一种治疗通过拮抗组胺H3受体可治疗的紊乱或病症的方法，该方法包括向需要此类治疗的哺乳动物投与上述式I化合物；以及治疗所选组中的紊乱或病症的方法，所选组包括抑郁症、情绪障碍、精神分裂症、焦虑症、阿尔茨海默病、注意力缺陷多动障碍（ADHD）、精神病性疾病、认知障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸系统疾病、过敏、过敏性气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、胃肠道疾病、胃肠道高低运动和酸性分泌，该方法包括向需要此类治疗的哺乳动物投与上述式I化合物。
• Histamine-3 Receptor Antagonists
  申请人：Wager Travis T.

  公开号：US20120220568A1

  公开（公告）日：2012-08-30

  This invention is directed to a compound of formula I, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 and n are as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a process of preparation of a compound of formula I, a method of treatment of a disorder or condition such as depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit hyperactivity disorder (ADHD), psychotic disorders, cognitive disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above.

  本发明涉及一种式子为I的化合物，其中R1、R2、R4、R5、R6、R7、R8和n如此定义，或其药学上可接受的盐；一种含有式I化合物的制药组合物，一种制备式I化合物的方法，一种治疗抑郁症、情绪障碍、精神分裂症、焦虑症、阿尔茨海默病、注意力缺陷多动障碍（ADHD）、精神病性疾病、认知障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸系统疾病、过敏、过敏诱发的气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、消化道疾病、胃肠道高低动力和酸性分泌物疾病的方法，该方法包括向需要此类治疗的哺乳动物给予上述式I化合物。
• US8314139B2
  申请人：——

  公开号：US8314139B2

  公开（公告）日：2012-11-20
• US8389743B2
  申请人：——

  公开号：US8389743B2

  公开（公告）日：2013-03-05
• [EN] HISTAMINE H3 RECEPTOR ANTAGONISTS/INVERSE AGONISTS FOR THE TREATMENT OF AUTISM SPECTRUM DISORDER<br/>[FR] ANTAGONISTES/AGONISTES INVERSES DU RÉCEPTEUR H3 DE L'HISTAMINE POUR LE TRAITEMENT D'UN TROUBLE DU SPECTRE AUTISTIQUE
  申请人：[en]RICHTER GEDEON NYRT.

  公开号：WO2022113008A1

  公开（公告）日：2022-06-02

  The present invention relates to a histamine H3 receptor antagonist/inverse agonist for use in the therapeutic treatment of autism spectrum disorder (ASD). The present invention relates to pharmaceutical compositions for administering to a patient a therapeutically effective amount of a histamine H3 receptor antagonist/inverse agonist. In order to assess the potential of histamine H3 receptor antagonist/inverse agonist compounds, among others GSK-189254 and LML-134 were investigated in the prenatal valproate model of ASD in rats and LML-134 was investigated in BALB/C mice. Surprisingly, it has been found that compounds characterized by this particular molecular mechanism of action showed great benefit in said animal model(s) that recapitulate(s) the symptoms of ASD.