(+)-(1S)-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo-[a,d]cyclohepten]-3-one | 1111640-44-8

• 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)-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo-[a,d]cyclohepten]-3-one
• 英文别名: (1S)-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-one；(3S)-spiro[cyclopentane-3,9'-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaene]-1-one
• CAS: 1111640-44-8
• 化学式: C₁₉H₁₈O
• 分子量: 262.351
• InChiKey: ZCXCCHRKHAXWIW-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (+)-(1S)-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo-[a,d]cyclohepten]-3-one 、 3-甲酸甲酯氮杂环丁烷盐酸盐 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 methyl 1-((1S)-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl)-3-azetidinecarboxylate
  参考文献：
  名称：

  Asymmetric route to spirotetracyclic (1S)-5′,11′-dihydro-3H-spiro[cyclopentane-1,10′-dibenzo[a,d]cyclohepten]-3-one derivatives

  摘要：

  A new synthetic pathway to the final compound 1-[(1S)-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl]-3-azetidinecarboxylic acid (1) was set up. The two preparative chiral HPLC separations needed in the first route were successfully avoided and replaced by two diastereomeric crystallizations of intermediate compounds 5 and 10. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.11.039
• 作为产物：
  描述：

  ethyl 3-oxo-(1S)-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cycloheptene]-2-carboxylate 在 4-二甲氨基吡啶 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以83%的产率得到(+)-(1S)-5',11'-dihydro-3H-spiro[cyclopentane-1,10'-dibenzo-[a,d]cyclohepten]-3-one
  参考文献：
  名称：

  Asymmetric route to spirotetracyclic (1S)-5′,11′-dihydro-3H-spiro[cyclopentane-1,10′-dibenzo[a,d]cyclohepten]-3-one derivatives

  摘要：

  A new synthetic pathway to the final compound 1-[(1S)-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl]-3-azetidinecarboxylic acid (1) was set up. The two preparative chiral HPLC separations needed in the first route were successfully avoided and replaced by two diastereomeric crystallizations of intermediate compounds 5 and 10. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.11.039

文献信息

• Novel Spirotetracyclic Zwitterionic Dual H₁/5-HT_2A Receptor Antagonists for the Treatment of Sleep Disorders
  作者：Massimo Gianotti、Maurizio Botta、Stephen Brough、Renzo Carletti、Emiliano Castiglioni、Corrado Corti、Michele Dal-Cin、Sonia Delle Fratte、Denana Korajac、Marija Lovric、Giancarlo Merlo、Milan Mesic、Francesca Pavone、Laura Piccoli、Slavko Rast、Maja Roscic、Anna Sava、Mario Smehil、Luigi Stasi、Andrea Togninelli、Mark J. Wigglesworth

  DOI：10.1021/jm100856p

  日期：2010.11.11

  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.
• Asymmetric route to spirotetracyclic (1S)-5′,11′-dihydro-3H-spiro[cyclopentane-1,10′-dibenzo[a,d]cyclohepten]-3-one derivatives
  作者：Massimo Gianotti、Daniele Andreotti、Davide Casotto、Mario Mattioli、Anna Mingardi、Francesca Pavone、Roberto Profeta、Filippo Valente

  DOI：10.1016/j.tetlet.2010.11.039

  日期：2011.1

  A new synthetic pathway to the final compound 1-[(1S)-5',11'-dihydrospiro[cyclopentane-1,10'-dibenzo[a,d]cyclohepten]-3-yl]-3-azetidinecarboxylic acid (1) was set up. The two preparative chiral HPLC separations needed in the first route were successfully avoided and replaced by two diastereomeric crystallizations of intermediate compounds 5 and 10. (C) 2010 Elsevier Ltd. All rights reserved.