diethyl 2-(5-oxo-7,8-dihydro-6H-naphthalen-2-yl)propanedioate | 158094-30-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: diethyl 2-(5-oxo-7,8-dihydro-6H-naphthalen-2-yl)propanedioate
• CAS: 158094-30-5
• 化学式: C₁₇H₂₀O₅
• 分子量: 304.343
• InChiKey: LCRYIXXZPITDFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl 2-(5-oxo-7,8-dihydro-6H-naphthalen-2-yl)propanedioate 在 硫酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 1-tetralone-6-acetic acid
  参考文献：
  名称：

  Selective .kappa.-Opioid Agonists: Synthesis and Structure-Activity Relationships of Piperidines Incorporating an Oxo-Containing Acyl Group

  摘要：

  This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using K-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2-naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED(50)s of 0.47 and 0.73 mu mol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective K-agonists, has a reduced propensity to cause a number of K-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED(50) Of 26.5 mu mol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

  DOI：

  10.1021/jm00047a006
• 作为产物：
  描述：

  N-(5-氧代-5,6,7,8-四氢萘酚-2-基)乙酰胺 在 氢溴酸 、 sodium hydride 、 copper(I) bromide 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 10.0h， 生成 diethyl 2-(5-oxo-7,8-dihydro-6H-naphthalen-2-yl)propanedioate
  参考文献：
  名称：

  Selective .kappa.-Opioid Agonists: Synthesis and Structure-Activity Relationships of Piperidines Incorporating an Oxo-Containing Acyl Group

  摘要：

  This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using K-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2-naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED(50)s of 0.47 and 0.73 mu mol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective K-agonists, has a reduced propensity to cause a number of K-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED(50) Of 26.5 mu mol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

  DOI：

  10.1021/jm00047a006