cis-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide | 935839-76-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: cis-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide
• CAS: 935839-76-2
• 化学式: C₁₇H₂₃ClN₂O
• 分子量: 306.835
• InChiKey: XRMDMTCGEGVPTG-GASCZTMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.18
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  32.34
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  (4-bromo-2-chlorophenyl)(pyrrolidin-1-yl)methanone 在 Wilkinson's catalyst 、 正丁基锂 、 硼烷四氢呋喃络合物 、 氢气 、 1-丙基磷酸酐 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， -78.0~75.0 ℃ 、310.27 kPa 条件下， 反应 59.42h， 生成 trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide 、 cis-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide
  参考文献：
  名称：

  Discovery of Two Clinical Histamine H₃ Receptor Antagonists: trans-N-Ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-Fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764)

  摘要：

  The discovery of two histamine H-3 antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-03654746) and 7 (PF-03654764) required five hypothesis driven design cycles. The key to success in identifying these clinical candidates was the development of a compound design strategy that leveraged medicinal chemistry knowledge and traditional assays in conjunction with computational and in vitro safety tools. Overall, clinical compounds 6 and 7 exceeded conservative safety margins and possessed optimal pharmacological and pharmacokinetic profiles, thus achieving our initial goal of identifying compounds with fully aligned oral drug attributes, "best-in-class" molecules.

  DOI：

  10.1021/jm200939b

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。
• US8158673B2
  申请人：——

  公开号：US8158673B2

  公开（公告）日：2012-04-17
• US8389743B2
  申请人：——

  公开号：US8389743B2

  公开（公告）日：2013-03-05
• [EN] HISTAMINE-3 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS DE L'HISTAMINE H3
  申请人：PFIZER PROD INC

  公开号：WO2007049123A1

  公开（公告）日：2007-05-03

  [EN] This invention is directed to a compound of formula Ias 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.
  [FR] Cette invention concerne un composé de formule I telle que définie ici ou un sel acceptable du point de vue pharmaceutique de celui-ci ; une composition pharmaceutique contenant un composé de formule I, un procédé de préparation d'un composé de formule I, un procédé de traitement d'un trouble ou d'une affection qui peut être traité en inhibant les récepteurs de l'histamine H3, ledit procédé comprenant d'administrer à un mammifère qui a besoin d'un tel traitement un composé de formule I tel que décrit ci-dessus, et un procédé de traitement d'un trouble ou d'une affection sélectionné dans le groupe constitué de la dépression, de troubles de l'humeur, de la schizophrénie, de troubles de l'anxiété, de la maladie d'Alzheimer, du trouble déficitaire de l'attention avec hyperactivité (TDAH), de troubles psychotiques, de troubles cognitifs, de troubles du sommeil, de l'obésité, de vertiges, de l'épilepsie, du mal des transports, de maladies respiratoires, de l'allergie, de réponses des voies respiratoires induites par une allergie, de la rhinite allergique, de l'obstruction nasale, de la congestion allergique, de la congestion, de l'hypotension, de maladies cardiovasculaires, de maladies du tractus gastro-intestinal, de l'hypermotilité et de l'hypomotilité et de la sécrétion acide du tractus gastro-intestinal, ledit procédé comprenant d'administrer à un mammifère qui a besoin d'un tel traitement un composé de formule I tel que décrit ci-dessus.