2-[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]acetyl chloride | 717111-93-8

• 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: 2-[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]acetyl chloride
• CAS: 717111-93-8
• 化学式: C₁₄H₁₇Cl₂NO
• 分子量: 286.201
• InChiKey: SNPWXPIQEHOSIU-WCQYABFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-苯丙醇 、 2-[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]acetyl chloride 在 吡啶 作用下， 以 氯仿 为溶剂， 反应 1.5h， 以87 mg的产率得到[(3R,4S)-4-(4-Chloro-phenyl)-1-methyl-piperidin-3-yl]-acetic acid 3-phenyl-propyl ester
  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：

  (3R,4S)-4-(4-chlorophenyl)-1-methylpiperidine-3-carbonyl chloride 在 盐酸 、 草酰氯 、 silver benzoate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 19.5h， 生成 2-[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]acetyl chloride
  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.