3-(3-Hydroxy-phenyl)-2-methyl-1-phenethyl-piperidine-3-carboxylic acid ethyl ester | 115982-14-4

• 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: 3-(3-Hydroxy-phenyl)-2-methyl-1-phenethyl-piperidine-3-carboxylic acid ethyl ester
• 英文别名: ethyl (2S,3S)-3-(3-hydroxyphenyl)-2-methyl-1-(2-phenylethyl)piperidine-3-carboxylate
• CAS: 115982-14-4
• 化学式: C₂₃H₂₉NO₃
• 分子量: 367.488
• InChiKey: TWPQKUQOAZWKSV-FDDCHVKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-(m-methoxyphenyl)-3-amino>butanoate 在 盐酸 、 三溴化硼 、 potassium hydride 、 potassium hydrogencarbonate 、 sodium iodide 作用下， 以 吡啶 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 71.0h， 生成 3-(3-Hydroxy-phenyl)-2-methyl-1-phenethyl-piperidine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Effects of addition of a 2-methyl group to ethyl nipecotates (.beta.-meperidines) on receptor affinities and opiate agonist/antagonist activities

  摘要：

  A series of 2-methyl-3-carbethoxy-3-(m-hydroxyphenyl)piperidine opiates (13a-d) with N-substituent variations have been synthesized, and their receptor affinities and in vivo agonist and antagonist activities and energy-conformational profiles have been determined. These are racemates of the alpha-epimer at the C-2 position, with a methyl group cis to the 3-phenyl group. One of the main goals of this study was to compare the conformational and pharmacological behavior of these 2-methyl "beta-meperidine" analogues to their 2-desmethyl racemic counterparts (14a-c) previously reported in the literature. The 2-desmethyl and 2-methyl analogues were found to have very similar phenyl equatorial conformers as their lowest energy forms with the addition of a 2-methyl group diminishing conformational flexibility. The presence of the 2-methyl group appears to diminish affinity at the mu-receptor and also to somewhat diminish already weak antinociceptic agonist activity. Given the similarity in lowest energy conformation, this reduction is most likely caused by the unfavorable interaction of the methyl group itself with a local mu-receptor binding site. Superposition of the phenol OH and protonated amine nitrogen NH of either 2-methyl enantiomer of 13a in its lowest energy conformer with the same OH and NH groups of metazocine, used as a high affinity rigid analogue, leads to reasonable overlap. However, the N-substituents and the piperidine and phenyl rings do not overlap in this proposed pharmacophore, perhaps accounting for the rather poor affinities found for these 3-phenylpiperidines and the lack of N-substituent modulation of affinity and efficacy as in fused ring opioids.

  DOI：

  10.1021/jm00118a028

文献信息

• Effects of addition of a 2-methyl group to ethyl nipecotates (.beta.-meperidines) on receptor affinities and opiate agonist/antagonist activities
  作者：John A. Lawson、Alice Cheng、Joseph DeGraw、Gernot Frenking、Edward Uyeno、Lawrence Toll、Gilda H. Loew

  DOI：10.1021/jm00118a028

  日期：1988.10

  A series of 2-methyl-3-carbethoxy-3-(m-hydroxyphenyl)piperidine opiates (13a-d) with N-substituent variations have been synthesized, and their receptor affinities and in vivo agonist and antagonist activities and energy-conformational profiles have been determined. These are racemates of the alpha-epimer at the C-2 position, with a methyl group cis to the 3-phenyl group. One of the main goals of this study was to compare the conformational and pharmacological behavior of these 2-methyl "beta-meperidine" analogues to their 2-desmethyl racemic counterparts (14a-c) previously reported in the literature. The 2-desmethyl and 2-methyl analogues were found to have very similar phenyl equatorial conformers as their lowest energy forms with the addition of a 2-methyl group diminishing conformational flexibility. The presence of the 2-methyl group appears to diminish affinity at the mu-receptor and also to somewhat diminish already weak antinociceptic agonist activity. Given the similarity in lowest energy conformation, this reduction is most likely caused by the unfavorable interaction of the methyl group itself with a local mu-receptor binding site. Superposition of the phenol OH and protonated amine nitrogen NH of either 2-methyl enantiomer of 13a in its lowest energy conformer with the same OH and NH groups of metazocine, used as a high affinity rigid analogue, leads to reasonable overlap. However, the N-substituents and the piperidine and phenyl rings do not overlap in this proposed pharmacophore, perhaps accounting for the rather poor affinities found for these 3-phenylpiperidines and the lack of N-substituent modulation of affinity and efficacy as in fused ring opioids.