methyl 1-(2'-fluoro-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-1,2,5,6-tetrahydro-3-pyridinecarboxylate | 1111639-99-6

• 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: methyl 1-(2'-fluoro-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-1,2,5,6-tetrahydro-3-pyridinecarboxylate
• 英文别名: methyl 1-(2'-fluoro-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-1,2,5,6-tetrahydropyridine-3-carboxylate；methyl 1-(6'-fluorospiro[cyclopentane-3,10'-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaene]-1-yl)-3,6-dihydro-2H-pyridine-5-carboxylate
• CAS: 1111639-99-6
• 化学式: C₂₆H₂₈FNO₂
• 分子量: 405.512
• InChiKey: UKNDBOUIMXGZBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-(2'-fluoro-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-1,2,5,6-tetrahydro-3-pyridinecarboxylate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 1-(2'-fluoro-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid
  参考文献：
  名称：

  [EN] SPIRO CYCLOPENTANE COMPOUNDS USEFUL AS ANTAGONISTS OF THE H1-RECEPTOR
  [FR] NOUVEAUX COMPOSÉS

  摘要：

  该发明涉及公式（I）的新颖螺环戊烷衍生物或其药用盐，用于治疗中枢神经系统（CNS）的疾病和病症，特别是睡眠障碍。

  公开号：

  WO2009016084A1
• 作为产物：
  描述：

  2'-fluoro-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-one 、 1,2,5,6-四氢吡啶-3-甲酸甲酯盐酸盐 在 N,N-二异丙基乙胺 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 碳酸氢钠 作用下， 以 1,2-二氯乙烷 、 二氯甲烷 为溶剂， 反应 0.17h， 生成 methyl 1-(2'-fluoro-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-1,2,5,6-tetrahydro-3-pyridinecarboxylate
  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

• Novel compounds
  申请人：Castiglioni Emiliano

  公开号：US20100190764A1

  公开（公告）日：2010-07-29

  This invention relates to novel Spiro cyclopentane derivatives of formula (I) or a pharmaceutically acceptable salt thereof, for treating diseases and conditions of the central nervous system (CNS), in particular sleep disorders.

  本发明涉及式(I)的新颖螺环戊烷衍生物或其药学上可接受的盐，用于治疗中枢神经系统(CNS)的疾病和病状，特别是睡眠障碍。