methyl 2-cyano-2-[9-(4-fluorophenyl)-6-oxaspiro[4.5]decan-9-yl]acetate | 1401031-17-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-cyano-2-[9-(4-fluorophenyl)-6-oxaspiro[4.5]decan-9-yl]acetate
• CAS: 1401031-17-1
• 化学式: C₁₉H₂₂FNO₃
• 分子量: 331.387
• InChiKey: KBGXRBNNZAIPTJ-UHFFFAOYSA-N

物化性质

• 沸点：
  469.2±35.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-cyano-2-[9-(4-fluorophenyl)-6-oxaspiro[4.5]decan-9-yl]acetate 在 potassium hydroxide 作用下， 以 甲醇 、 乙二醇 、 二乙胺 为溶剂， 反应 3.0h， 生成 2-[(9S)-9-(4-fluorophenyl)-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
• 作为产物：
  描述：

  6-oxaspiro[4.5]decan-9-one 在 copper(l) iodide 、 ammonium acetate 、 溶剂黄146 作用下， 以 乙醚 、 苯 为溶剂， 反应 3.5h， 生成 methyl 2-cyano-2-[9-(4-fluorophenyl)-6-oxaspiro[4.5]decan-9-yl]acetate
  参考文献：
  名称：

  OPIOID RECEPTOR LIGANDS AND METHODS OF USING AND MAKING SAME

  摘要：

  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。

  公开号：

  US20120245181A1

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。
• [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。
• Opioid receptor ligands and methods of using and making same
  申请人：Yamashita Dennis

  公开号：US09044469B2

  公开（公告）日：2015-06-02

  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.

  这份申请描述了一些可作为阿片受体配体的化合物，这些化合物可用于治疗例如疼痛和与疼痛相关的疾病。
• Opioid Receptor Ligands and Methods of Using and Making Same
  申请人：Yamashita Dennis

  公开号：US20130331408A1

  公开（公告）日：2013-12-12

  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疼痛相关疾病。
• Opioid Receptor Ligands And Methods Of Using And Making Same
  申请人：Trevena, Inc.

  公开号：US20150246904A1

  公开（公告）日：2015-09-03

  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.

  这份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相关的疾病。