2-(2,3-dihydro-1H-inden-5-yl)-1-morpholin-4-ylethanethione | 158094-20-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(2,3-dihydro-1H-inden-5-yl)-1-morpholin-4-ylethanethione
• CAS: 158094-20-3
• 化学式: C₁₅H₁₉NOS
• 分子量: 261.388
• InChiKey: DLVRFPCSJRGBFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  44.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2,3-dihydro-1H-inden-5-yl)-1-morpholin-4-ylethanethione 在 氢氧化钾 作用下， 反应 20.0h， 以75%的产率得到2,3-二氢-1H-茚-5-乙酸
  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：

  茚满 、 alkaline earth salt of/the/ methylsulfuric acid 在 三氯化铝 、 sulfur 作用下， 以 二氯甲烷 为溶剂， 反应 39.0h， 生成 2-(2,3-dihydro-1H-inden-5-yl)-1-morpholin-4-ylethanethione
  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

文献信息

• Selective .kappa.-Opioid Agonists: Synthesis and Structure-Activity Relationships of Piperidines Incorporating an Oxo-Containing Acyl Group
  作者：Giuseppe Giardina、Geoffrey D. Clarke、Giulio Dondio、Giuseppe Petrone、Massimo Sbacchi、Vittorio Vecchietti

  DOI：10.1021/jm00047a006

  日期：1994.10

  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.