2',3',4',9'-tetrahydro- N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'-pyrido[3,4-b]indol]-4-amine | 1357001-58-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 2',3',4',9'-tetrahydro- N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'-pyrido[3,4-b]indol]-4-amine
• 英文别名: 2',3',4',9'-tetrahydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'-pyrido[3,4-b]indol]-4-amine；trans-2',3',4',9'-tetrahydro-N,N-dimethyl-4-phenylspiro[cyclohexane-1,1'(1'H)-pyrido[3,4-b]indole]-4-amine
• CAS: 1357001-58-1
• 化学式: C₂₄H₂₉N₃
• 分子量: 359.514
• InChiKey: FPSHFESBMNTMNM-RQNOJGIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  27.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  31.06
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2',3',4',9'-tetrahydro- N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'-pyrido[3,4-b]indol]-4-amine 在 三甲基氯硅烷 、 水 作用下， 以 丁酮 为溶剂， 以670 mg的产率得到2',3',4',9'-tetrahydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'-pyrido[3,4-b]indol]-4-amine dihydrochloride
  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 、 氧气 、 sodium sulfate 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 114.0h， 生成 2',3',4',9'-tetrahydro- N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'-pyrido[3,4-b]indol]-4-amine
  参考文献：
  名称：

  Cis-tetrahydro-spiro(cyclohexane-1,1'-pyrido[3,4-b]indole)-4-amine Compounds

  摘要：

  Cis-四氢噻吡啶并[环己烷-1,1′-吡啶并[3,4-b]吲哚]-4-胺化合物作用于痛觉素/ORL-1受体系统以及μ-阿片受体系统，特别以其在治疗慢性疼痛（如炎症性疼痛、内脏疼痛、肿瘤疼痛和神经病理性疼痛）方面的选择性有效性而著称，同时不会对急性、痛觉性疼痛表现出显著的有效性。

  公开号：

  US20120029006A1

文献信息

• Cis-tetrahydro-spiro(cyclohexane-1,1'-pyrido[3,4-b]indole)-4-amine Compounds
  申请人：Linz Klaus

  公开号：US20120029006A1

  公开（公告）日：2012-02-02

  Cis-tetrahydro-spiro(cyclohexane-1,1′-pyrido[3,4-b]indole)-4-amine compounds which act on the nociceptin/ORL-1 receptor system as well as on the μ-opioid receptor system and which are distinguished in particular by selective effectiveness in the treatment of chronic pain, such as inflammatory pain, visceral pain, tumour pain, and neuropathic pain, without at the same time developing pronounced effectiveness against acute, nociceptive pain.

  Cis-四氢噻吡啶并[环己烷-1,1′-吡啶并[3,4-b]吲哚]-4-胺化合物作用于痛觉素/ORL-1受体系统以及μ-阿片受体系统，特别以其在治疗慢性疼痛（如炎症性疼痛、内脏疼痛、肿瘤疼痛和神经病理性疼痛）方面的选择性有效性而著称，同时不会对急性、痛觉性疼痛表现出显著的有效性。
• Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol
  作者：Stefan Schunk、Klaus Linz、Claudia Hinze、Sven Frormann、Stefan Oberbörsch、Bernd Sundermann、Saskia Zemolka、Werner Englberger、Tieno Germann、Thomas Christoph、Babette-Y. Kögel、Wolfgang Schröder、Stephanie Harlfinger、Derek Saunders、Achim Kless、Hans Schick、Helmut Sonnenschein

  DOI：10.1021/ml500117c

  日期：2014.8.14

  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.