4-dimethylamino-1-[3-(1H-indol-3-yl)propyl]-4-phenylcyclohexanol | 1189758-87-9

• 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-dimethylamino-1-[3-(1H-indol-3-yl)propyl]-4-phenylcyclohexanol
• 英文别名: 4-(dimethylamino)-1-[3-(1H-indol-3-yl)propyl]-4-phenylcyclohexan-1-ol
• CAS: 1189758-87-9
• 化学式: C₂₅H₃₂N₂O
• 分子量: 376.542
• InChiKey: KONBMGXVHCEHJP-UHFFFAOYSA-N

物化性质

• 沸点：
  556.1±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  39.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-dimethylamino-1-[3-(1H-indol-3-yl)propyl]-4-phenylcyclohexanol 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 以18%的产率得到2,3,4,9-tetrahydro-N,N-dimethyl-4'-phenyl-spiro[carbazole-1,1'-cyclohexane]-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
• 作为产物：
  描述：

  4-dimethylamino-4-phenyl-1-(5-triethylsilanyl-pent-4-inyl)cyclohexanol 在 [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride 、 四丁基氟化铵 、 sodium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-dimethylamino-1-[3-(1H-indol-3-yl)propyl]-4-phenylcyclohexanol
  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

• SPIRO(5.5)UNDECANE DERIVATIVES
  申请人：ZEMOLKA Saskia

  公开号：US20090247505A1

  公开（公告）日：2009-10-01

  The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.

  这项发明涉及具有与μ-阿片受体和ORL 1-受体亲和性的化合物，其生产方法，含有这些化合物的药物以及利用这些化合物治疗疼痛和其他疾病的用途。
• Spiro(5.5)undecane derivatives
  申请人：Grunenthal GmbH

  公开号：US08288430B2

  公开（公告）日：2012-10-16

  The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.

  本发明涉及具有对μ-阿片受体和ORL 1-受体亲和力的化合物，其制备方法，含有这些化合物的药物以及利用这些化合物治疗疼痛和其他疾病的用途。
• SPIRO(5.5)UNDECAN DERIVATE
  申请人：Grünenthal GmbH

  公开号：EP2257526A1

  公开（公告）日：2010-12-08
• US8288430B2
  申请人：——

  公开号：US8288430B2

  公开（公告）日：2012-10-16
• [DE] SPIRO(5.5)UNDECAN DERIVATE<br/>[EN] SPIRO(5.5)UNDECANE DERIVATIVES<br/>[FR] DÉRIVÉS DE SPIRO(5.5)UNDÉCANE
  申请人：GRUENENTHAL GMBH

  公开号：WO2009118169A1

  公开（公告）日：2009-10-01

  Die Erfindung betrifft Verbindungen, welche eine Affinität an den μ-Opioid-Rezeptor und den ORL1-Rezeptor aufweisen, Verfahren zu deren Herstellung, Arzneimittel enthaltend diese Verbindungen und die Verwendung dieser Verbindungen zur Herstellung von Arzneimitteln.