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

• 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 dihydrochloride
• 化学式: C₂₄H₂₉N₃*2ClH
• 分子量: 432.436
• InChiKey: RUYCAYIZLOVUHR-FBGQUBCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.96
• 重原子数：
  28.0
• 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

• 作为产物：
  描述：

  4-dimethylamino-4-phenylcyclohexanone, ethylene ketal hydrochloride 在 盐酸 、 三甲基氯硅烷 、 水 、 三氟乙酸 作用下， 以 乙醚 、 1,2-二氯乙烷 、 丁酮 为溶剂， 生成 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

文献信息

• 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.