2-[(9S)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]acetonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-[(9S)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]acetonitrile
• 英文别名: (S)-2-(9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl)acetonitrile；2-[(9S)-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]acetonitrile
• 化学式: C₁₆H₂₀N₂O
• 分子量: 256.348
• InChiKey: AJVYDBCIZBRGAK-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  45.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(9S)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]acetonitrile 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 2-[(9S)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethan-1-amine
  参考文献：
  名称：

  Structure–Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain

  摘要：

  The concept of "ligand bias" at G protein coupled receptors has been introduced to describe ligands which preferentially stimulate one intracellular signaling pathway over another. There is growing interest in developing biased G protein coupled receptor ligands to yield safer, better tolerated, and more efficacious drugs. The classical mu opioid morphine elicited increased efficacy and duration of analgesic response with reduced side effects in fl-arrestin-2 knockout mice compared to wild-type mice, suggesting that G protein biased p opioid receptor agonists would be more efficacious with reduced adverse events. Here we describe our efforts to identify a potent, selective, and G protein biased p opioid receptor agonist, TRV130 ((R)-30). This novel molecule demonstrated an improved therapeutic index (analgesia vs adverse effects) in rodent models and characteristics appropriate for clinical development. It is currently being evaluated in human clinical trials for the treatment of acute severe pain.

  DOI：

  10.1021/jm4010829
• 作为产物：
  描述：

  6-oxaspiro[4.5]decan-9-one 在 copper(l) iodide 、 ammonium acetate 、 溶剂黄146 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙二醇 、 二乙胺 、 苯 为溶剂， 反应 3.5h， 生成 2-[(9S)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]acetonitrile
  参考文献：
  名称：

  Structure–Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain

  摘要：

  The concept of "ligand bias" at G protein coupled receptors has been introduced to describe ligands which preferentially stimulate one intracellular signaling pathway over another. There is growing interest in developing biased G protein coupled receptor ligands to yield safer, better tolerated, and more efficacious drugs. The classical mu opioid morphine elicited increased efficacy and duration of analgesic response with reduced side effects in fl-arrestin-2 knockout mice compared to wild-type mice, suggesting that G protein biased p opioid receptor agonists would be more efficacious with reduced adverse events. Here we describe our efforts to identify a potent, selective, and G protein biased p opioid receptor agonist, TRV130 ((R)-30). This novel molecule demonstrated an improved therapeutic index (analgesia vs adverse effects) in rodent models and characteristics appropriate for clinical development. It is currently being evaluated in human clinical trials for the treatment of acute severe pain.

  DOI：

  10.1021/jm4010829

文献信息

• [EN] COMBINATIONS OF OPIOID RECEPTOR LIGANDS AND CYTOCHROME P450 INHIBITORS<br/>[FR] COMBINAISONS DE LIGANDS DE RÉCEPTEURS OPIOÏDES ET D'INHIBITEURS DU CYTOCHROME P450
  申请人：TREVENA INC

  公开号：WO2017106547A1

  公开（公告）日：2017-06-22

  This application described compounds that can act as opioid receptor ligands, and compositions comprising the compounds and cytochrome P450 inhibitors, which can be used in the treatment of, for example, pain and pain related disorders.

  这种应用描述了可以作为阿片受体配体的化合物，以及包含这些化合物和细胞色素P450抑制剂的组合物，可以用于治疗例如疼痛和与疼痛相关的疾病。
• 阿片受体激动剂及其应用
  申请人：四川海思科制药有限公司

  公开号：CN109206417B

  公开（公告）日：2023-01-03

  本申请描述了可以用作阿片受体配体的化合物及其盐，及制备方法和含有该化合物的组合物，及其可以作为μ阿片受体激动剂的用途，用于治疗μ阿片受体介导的相关疾病，如疼痛和疼痛相关的紊乱。
• [EN] DEUTERATED COMPOUNDS FOR TREATING PAIN<br/>[FR] COMPOSÉS DEUTÉRÉS POUR TRAITER LA DOULEUR
  申请人：NEUFORM PHARMACEUTICALS INC

  公开号：WO2018006077A1

  公开（公告）日：2018-01-04

  The invention provides novel chemical compounds useful for treating pain or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.

  这项发明提供了一种新型化合物，可用于治疗疼痛或相关疾病或障碍，以及其制备和使用的药物组合物和方法。
• OPIOID RECEPTOR LIGANDS AND METHODS OF USING AND MAKING SAME
  申请人：Yamashita Dennis

  公开号：US20120245181A1

  公开（公告）日：2012-09-27

  This application describes compounds that can act as opioid receptor ligands, which compounds can be used in the treatment of, for example, pain and pain related disorders.

  这种应用描述了可以作为阿片受体配体的化合物，这些化合物可以用于治疗例如疼痛和与疼痛相关的疾病。
• [EN] OPIOID RECEPTOR LIGANDS AND METHODS OF USING AND MAKING SAME<br/>[FR] LIGANDS DE RÉCEPTEURS OPÏOIDES, ET LEURS PROCÉDÉS D'UTILISATION ET DE PRODUCTION
  申请人：TREVENA INC

  公开号：WO2012129495A1

  公开（公告）日：2012-09-27

  This application describes compounds that can act as opioid receptor ligands, which compounds can be used in the treatment of, for example, pain and pain related disorders.

  这个申请描述了一些可以作为阿片受体配体的化合物，这些化合物可以用于治疗例如疼痛和与疼痛有关的疾病。