5-<(methoxycarbonyl)methyl>-γ-oxo-2-thiophenebutyric acid | 158094-22-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 5-<(methoxycarbonyl)methyl>-γ-oxo-2-thiophenebutyric acid
• 英文别名: 4-[5-(2-Methoxy-2-oxoethyl)thiophen-2-yl]-4-oxobutanoic acid
• CAS: 158094-22-5
• 化学式: C₁₁H₁₂O₅S
• 分子量: 256.279
• InChiKey: WLKZDSUAZDAMMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-<(methoxycarbonyl)methyl>-γ-oxo-2-thiophenebutyric acid 在 氢氧化钾 、 sodium hydroxide 、 乙酸酐 、 肼 作用下， 以 二乙二醇 为溶剂， 反应 2.75h， 生成 4-oxo-4.5.6.7-tetrahydrobenzothiophene-2-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：

  2-噻吩乙酸 在 三氯化铝 、 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 4.0h， 生成 5-<(methoxycarbonyl)methyl>-γ-oxo-2-thiophenebutyric 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