3-[(3R,4S)-4-(4-Chloro-phenyl)-1-methyl-piperidin-3-yl]-propan-1-ol | 717111-36-9

• 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-[(3R,4S)-4-(4-Chloro-phenyl)-1-methyl-piperidin-3-yl]-propan-1-ol
• 英文别名: 3-[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]propan-1-ol
• CAS: 717111-36-9
• 化学式: C₁₅H₂₂ClNO
• 分子量: 267.799
• InChiKey: QXYGLYJWXYAGSO-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[(3R,4S)-4-(4-Chloro-phenyl)-1-methyl-piperidin-3-yl]-propan-1-ol 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 以61%的产率得到(+)-4β-(4-Chlorophenyl)-3α-(3-fluoropropyl)-1-methylpiperidine
  参考文献：
  名称：

  Synthesis, Molecular Modeling, and Biological Studies of Novel Piperidine-Based Analogues of Cocaine:  Evidence of Unfavorable Interactions Proximal to the 3α-Position of the Piperidine Ring

  摘要：

  A qualitative model for the binding pocket proximal to the 3alpha-substituent of the piperidine-based monoamine transporter ligands was proposed and tested. Based on this model, a new series of druglike 3alpha-modified piperidine-based analogues of cocaine were designed, synthesized, and studied for their ability to inhibit reuptake of DA, 5-HT, and NE by the DA, 5-HT, and NE transporters. We found that the insertion of at least one additional methylene group between the piperidine ring and the polar group in the 3alpha-substituent dramatically improves the activity of the compounds that are generally inactive without this additional linker. Molecular modeling analysis showed that the more flexible 3alpha-substituents can avoid unfavorable interactions with the binding sites of DAT, SERT, and NET. The present results may have important implications for the elucidation of the structural differences between DA, 5-HT, and NE transporters and for the further design of new leads for development of cocaine abuse medication as well as certain neurological disorders such as ADHD and depression.

  DOI：

  10.1021/jm0303296
• 作为产物：
  描述：

  (+)-4β-(4-Chlorophenyl)-3α-(hydroxymethyl)-1-methylpiperidine 在 甲醇 、 lithium aluminium tetrahydride 、 草酰氯 、 sodium hydride 、 magnesium 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.58h， 生成 3-[(3R,4S)-4-(4-Chloro-phenyl)-1-methyl-piperidin-3-yl]-propan-1-ol
  参考文献：
  名称：

  Synthesis, Molecular Modeling, and Biological Studies of Novel Piperidine-Based Analogues of Cocaine:  Evidence of Unfavorable Interactions Proximal to the 3α-Position of the Piperidine Ring

  摘要：

  A qualitative model for the binding pocket proximal to the 3alpha-substituent of the piperidine-based monoamine transporter ligands was proposed and tested. Based on this model, a new series of druglike 3alpha-modified piperidine-based analogues of cocaine were designed, synthesized, and studied for their ability to inhibit reuptake of DA, 5-HT, and NE by the DA, 5-HT, and NE transporters. We found that the insertion of at least one additional methylene group between the piperidine ring and the polar group in the 3alpha-substituent dramatically improves the activity of the compounds that are generally inactive without this additional linker. Molecular modeling analysis showed that the more flexible 3alpha-substituents can avoid unfavorable interactions with the binding sites of DAT, SERT, and NET. The present results may have important implications for the elucidation of the structural differences between DA, 5-HT, and NE transporters and for the further design of new leads for development of cocaine abuse medication as well as certain neurological disorders such as ADHD and depression.

  DOI：

  10.1021/jm0303296

文献信息

• Synthesis, Molecular Modeling, and Biological Studies of Novel Piperidine-Based Analogues of Cocaine:  Evidence of Unfavorable Interactions Proximal to the 3α-Position of the Piperidine Ring
  作者：Pavel A. Petukhov、Jianrong Zhang、Cheng Z. Wang、Yan Ping Ye、Kenneth M. Johnson、Alan P. Kozikowski

  DOI：10.1021/jm0303296

  日期：2004.6.1

  A qualitative model for the binding pocket proximal to the 3alpha-substituent of the piperidine-based monoamine transporter ligands was proposed and tested. Based on this model, a new series of druglike 3alpha-modified piperidine-based analogues of cocaine were designed, synthesized, and studied for their ability to inhibit reuptake of DA, 5-HT, and NE by the DA, 5-HT, and NE transporters. We found that the insertion of at least one additional methylene group between the piperidine ring and the polar group in the 3alpha-substituent dramatically improves the activity of the compounds that are generally inactive without this additional linker. Molecular modeling analysis showed that the more flexible 3alpha-substituents can avoid unfavorable interactions with the binding sites of DAT, SERT, and NET. The present results may have important implications for the elucidation of the structural differences between DA, 5-HT, and NE transporters and for the further design of new leads for development of cocaine abuse medication as well as certain neurological disorders such as ADHD and depression.