11,11-di-2-propen-1-yl-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one | 1111640-37-9

• 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: 11,11-di-2-propen-1-yl-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one
• 英文别名: 10,10-bis(prop-2-enyl)tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-9-one
• CAS: 1111640-37-9
• 化学式: C₂₁H₂₀O
• 分子量: 288.389
• InChiKey: SNCQOLKZWNWRFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  11,11-di-2-propen-1-yl-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 二氯甲烷 为溶剂， 生成 spiro[cyclopent-3-ene-1,10'-dibenzo[a,d]cyclohepten]-11'(5'H)-one
  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：

  5,11-二氢-10H-二苯并[A,D][7]轮烯-10-酮 、 3-溴丙烯 在 potassium tert-butylate 作用下， 反应 1.75h， 生成 11,11-di-2-propen-1-yl-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one
  参考文献：
  名称：

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

  摘要：

  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。

  公开号：

  WO2009016085A1

文献信息

• Synthesis and structure–activity relationship of 2-(aminoalkyl)-3,3a,8,12b-tetrahydro-2H-dibenzocyclohepta[1,2-b]furan derivatives: a novel series of 5-HT2A/2C receptor antagonists
  作者：José Cid、José M. Alonso、José I. Andrés、Javier Fernández、Pilar Gil、Laura Iturrino、Encarna Matesanz、Theo F. Meert、Anton Megens、Victor K. Sipido、Andrés A. Trabanco

  DOI：10.1016/j.bmcl.2004.03.069

  日期：2004.6

  Following the program started at Johnson & Johnson Pharmaceutical Research & Development searching for 5-HT(2A/2C) antagonists we now report on the synthesis of a series of substituted 2-(aminomethyl)-3,3a,8,12b-tetrahydro-2H-dibenzocyclohepta[1,2-b]furan derivatives. The 5-HT2A, 5-HT2C and H1 receptor affinities of the described compounds are reported. The mCCP antagonistic activity of a set of selected

  在强生制药研究与开发计划开始寻找5-HT（2A / 2C）拮抗剂后，我们现在报告一系列取代的2-（氨基甲基）-3,3a，8,12b-tetrahydro- 2H-二苯并环庚[1,2-b]呋喃衍生物。报道了所述化合物的5-HT 2A，5-HT 2C和H 1受体亲和力。还报道了一组选定分子的mCCP拮抗活性。
• 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。
• Spiro Compounds Useful as Antagonists of the H1 Receptor
  申请人：Botta Maurizio

  公开号：US20100311734A1

  公开（公告）日：2010-12-09

  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I式或其药学上可接受的盐，用于治疗中枢神经系统（CNS）的疾病和症状，特别是睡眠障碍。
• 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.