Cyclopropylmethyl-methyl-(S)-1-piperidin-2-ylmethyl-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: Cyclopropylmethyl-methyl-(S)-1-piperidin-2-ylmethyl-amine
• 英文别名: 1-cyclopropyl-N-methyl-N-[[(2S)-piperidin-2-yl]methyl]methanamine
• 化学式: C₁₁H₂₂N₂
• 分子量: 182.309
• InChiKey: XRKPUQRWHQCBMT-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Cyclopropylmethyl-methyl-(S)-1-piperidin-2-ylmethyl-amine 、 2-(5-oxo-7,8-dihydro-6H-naphthalen-2-yl)acetyl chloride 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 6-(2-{(S)-2-[(Cyclopropylmethyl-methyl-amino)-methyl]-piperidin-1-yl}-2-oxo-ethyl)-3,4-dihydro-2H-naphthalen-1-one
  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.