trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide | 935839-86-4

• 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: trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide
• CAS: 935839-86-4
• 化学式: C₁₇H₂₃ClN₂O
• 分子量: 306.835
• InChiKey: XRMDMTCGEGVPTG-SHTZXODSSA-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

• 作为反应物：
  描述：

  trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-methylcyclobutanecarboxamide 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以77%的产率得到1-{trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutyl}-N-methylmethanamine
  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
• 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