4',9'-dihydro-N,N-dimethyl-4-phenyl-3'H-spiro[cyclohexane-1,1'-thiopyrano[3,4-b]-indol]-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4',9'-dihydro-N,N-dimethyl-4-phenyl-3'H-spiro[cyclohexane-1,1'-thiopyrano[3,4-b]-indol]-4-amine
• 英文别名: 1,1-(3-dimethylamino-3-phenylpentamethylene)-1,3,4,9-tetrahydro-2-thia-9-azafluoren；N,N-dimethyl-1'-phenylspiro[4,9-dihydro-3H-thiopyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine
• 化学式: C₂₄H₂₈N₂S
• 分子量: 376.566
• InChiKey: JCROKVWSGUVMAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4',9'-dihydro-N,N-dimethyl-4-phenyl-3'H-spiro[cyclohexane-1,1'-thiopyrano[3,4-b]-indol]-4-amine 、 柠檬酸 以 乙醇 为溶剂， 反应 20.17h， 以85 mg的产率得到4',9'-dihydro-N,N-dimethyl-4-phenyl-3'H-spiro[cyclohexane-1,1'-thiopyrano[3,4-b]-indol]-4-amine hemicitrate
  参考文献：
  名称：

  Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol

  摘要：

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

  DOI：

  10.1021/ml500117c
• 作为产物：
  描述：

  4-dimethylamino-4-phenylcyclohexanone, ethylene ketal hydrochloride 在 盐酸 、 水 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 4',9'-dihydro-N,N-dimethyl-4-phenyl-3'H-spiro[cyclohexane-1,1'-thiopyrano[3,4-b]-indol]-4-amine
  参考文献：
  名称：

  Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol

  摘要：

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

  DOI：

  10.1021/ml500117c

文献信息

• [DE] SPIROCYCLISCHE CYCLOHEXAN-DERIVATE<br/>[EN] SPIROCYCLIC CYCLOHEXANE DERIVATIVES<br/>[FR] DERIVES DE CYCLOHEXANE SPIROCYCLIQUES
  申请人：GRUENENTHAL GMBH

  公开号：WO2004043967A1

  公开（公告）日：2004-05-27

  Die vorliegende Erfindung betrifft spirocyclische Cyclohexan-Drerivate, Verfahren zu deren Herstellung, Arzneimittel enthaltend diese Verbindungen und die Verwendung von spirocyclischen Cyclohexan-Derivaten zur Herstellung von Arzneimitteln.

  这项发明涉及螺环状环己烷衍生物，其制备方法，包含这些化合物的药物以及使用螺环状环己烷衍生物制备药物的用途。
• Spirocyclic cyclohexane compounds
  申请人：Hinze Claudia

  公开号：US20060004034A1

  公开（公告）日：2006-01-05

  Spirocyclic cyclohexane compounds corresponding to formula I a method for producing them, pharmaceutical compositions containing them, and methods of using them.

  本发明涉及与式Ia相应的螺环式环己烷化合物的制备方法，包含它们的制药组合物以及使用它们的方法。
• Spirocyclic Cyclohexane Compounds
  申请人：Hinze Claudia

  公开号：US20100240897A1

  公开（公告）日：2010-09-23

  Spirocyclic cyclohexane compounds corresponding to formula I a method for producing them, pharmaceutical compositions containing them, and methods of using them.

  本发明涉及与式Ia相对应的螺环式环己烷化合物及其制备方法，包含它们的制药组合物和使用它们的方法。
• Process for Preparing Spirocyclic Cyclohexane Compounds, Compositions Containing Such Compounds and Method of Using Such Compounds
  申请人：HINZE Claudia

  公开号：US20110319440A1

  公开（公告）日：2011-12-29

  Spirocyclic cyclohexane compounds corresponding to formula I a method for producing them, pharmaceutical compositions containing them, and methods of using them.

  螺环状的环己烷化合物对应于公式Ia，制备它们的方法，包含它们的药物组合物以及使用它们的方法。
• Process for Preparing Spirocyclic Cyclohexane Compounds, Compositions Containing Such Compounds and Method of Using Such Compounds
  申请人：Gruenenthal GmbH

  公开号：US20150322080A1

  公开（公告）日：2015-11-12

  Spirocyclic cyclohexane compounds corresponding to formula I a method for producing them, pharmaceutical compositions containing them, and methods of using them.

  本发明涉及与Ia式相对应的螺环烷化合物的制备方法、含有它们的制药组合物以及使用它们的方法。