benzyl {2-[2,2-diethyl-4-(4-fluorophenyl)oxan-4-yl]ethyl}amine trifluoroacetate salt

• 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: benzyl {2-[2,2-diethyl-4-(4-fluorophenyl)oxan-4-yl]ethyl}amine trifluoroacetate salt
• 英文别名: N-benzyl-2-[2,2-diethyl-4-(4-fluorophenyl)oxan-4-yl]ethanamine;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₄H₃₂FNO
• 分子量: 483.547
• InChiKey: WGQNTCDCQSADCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.25
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl 2-cyano-2-[(4Z)-2,2-diethyloxan-4-ylidene]acetate 在 sodium tetrahydroborate 、 copper(l) iodide 、 lithium aluminium tetrahydride 、 sodium sulfate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 乙二醇 为溶剂， 反应 8.5h， 生成 benzyl {2-[2,2-diethyl-4-(4-fluorophenyl)oxan-4-yl]ethyl}amine trifluoroacetate salt
  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

• Structure–Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9<i>R</i>)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain
  作者：Xiao-Tao Chen、Philip Pitis、Guodong Liu、Catherine Yuan、Dimitar Gotchev、Conrad L. Cowan、David H. Rominger、Michael Koblish、Scott M. DeWire、Aimee L. Crombie、Jonathan D. Violin、Dennis S. Yamashita

  DOI：10.1021/jm4010829

  日期：2013.10.24

  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.