(1S,3R)-N,N-dimethyl-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-amine | 1111727-69-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: (1S,3R)-N,N-dimethyl-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-amine
• 英文别名: N,N-dimethyl-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-amine
• CAS: 1111727-69-5
• 化学式: C₂₁H₂₅N
• 分子量: 291.436
• InChiKey: IYDOAHOHMRQFTJ-CTNGQTDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  3.24
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为产物：
  描述：

  (+)-(1S)-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo-[a,d]cyclohepten]-3-one 、 二甲胺 在 溶剂黄146 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 作用下， 以 四氢呋喃 、 DCE 为溶剂， 反应 6.33h， 以5.1 mg的产率得到(1S,3R)-N,N-dimethyl-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-amine
  参考文献：
  名称：

  Novel Spirotetracyclic Zwitterionic Dual H₁/5-HT_2A Receptor Antagonists for the Treatment of Sleep Disorders

  摘要：

  Histamine H-1 and serotonin 5-HT2A receptors mediate two different mechanisms involved in sleep regulation: H-1 antagonists are sleep inducers, while 5-HT2A antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H-1/5-HT2A potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H-1/5-HT2A activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

  DOI：

  10.1021/jm100856p

文献信息

• [EN] SPIRO COMPOUNDS USEFUL AS ANTAGONISTS OF THE H1 RECEPTOR<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2009016085A1

  公开（公告）日：2009-02-05

  The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, for treating diseases and conditions of the central nervous system (CNS), in particular sleep disorders.

  该发明提供了化合物的公式(I)或其药学上可接受的盐，用于治疗中枢神经系统（CNS）疾病和症状，特别是睡眠障碍。