(3R,4R)-2-allyl-4-(3-(benzyloxy)phenyl)-3,4-dimethyl-piperidine

• 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: (3R,4R)-2-allyl-4-(3-(benzyloxy)phenyl)-3,4-dimethyl-piperidine
• 英文别名: (3R,4R)-3,4-dimethyl-4-(3-phenylmethoxyphenyl)-2-prop-2-enylpiperidine
• 化学式: C₂₃H₂₉NO
• 分子量: 335.489
• InChiKey: HCNITQMYEUEIGL-WUVXKSLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,4R)-2-allyl-4-(3-(benzyloxy)phenyl)-3,4-dimethyl-piperidine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 16.0h， 生成 (8R,9R,9aS)-8-(3-(benzyloxy)phenyl)-8,9-dimethyl-3-phenyl-7,8,9,9a-tetrahydro-1H-quinolizin-4(6H)-one
  参考文献：
  名称：

  Elucidation of the Bioactive Conformation of the N-Substituted trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Class of μ-Opioid Receptor Antagonists

  摘要：

  The series of trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidines have been widely investigated as opioid receptor antagonists. One of our research goals was to explore the bioactive conformation of the N-phenethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine derivative 3, prototypical A-opioid antagonist in this series. In this effort, the rotational degrees of freedom of the N-substituent of 3 were limited by incorporation of an ethylene bridge between the piperidine 2- or 6-position of 3 and the benzylic position of the N-phenethyl moiety. The overall modification led to a novel series of fused bicyclic derivatives of the octahydroquinolizine chemical class, conformationally restricted analogue of 3. The constrained analogues 6 and 9 showed high affinity toward the mu-opioid receptor. Compound 6 was found to be a mu-opioid antagonist, whereas the constrained analogue 9 displayed potent mu-agonist activity in vitro. This study provides additional information about the molecular determinants for mu recognition, the structural features affecting ligand binding, and the structure function relationships.

  DOI：

  10.1021/jm060486f
• 作为产物：
  描述：

  (+)-4(R)-(3-benzyloxyphenyl)-3(R),4-dimethylpiperidine 在 sodium tungstate 、 双氧水 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 19.5h， 生成 (3R,4R)-2-allyl-4-(3-(benzyloxy)phenyl)-3,4-dimethyl-piperidine
  参考文献：
  名称：

  Elucidation of the Bioactive Conformation of the N-Substituted trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Class of μ-Opioid Receptor Antagonists

  摘要：

  The series of trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidines have been widely investigated as opioid receptor antagonists. One of our research goals was to explore the bioactive conformation of the N-phenethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine derivative 3, prototypical A-opioid antagonist in this series. In this effort, the rotational degrees of freedom of the N-substituent of 3 were limited by incorporation of an ethylene bridge between the piperidine 2- or 6-position of 3 and the benzylic position of the N-phenethyl moiety. The overall modification led to a novel series of fused bicyclic derivatives of the octahydroquinolizine chemical class, conformationally restricted analogue of 3. The constrained analogues 6 and 9 showed high affinity toward the mu-opioid receptor. Compound 6 was found to be a mu-opioid antagonist, whereas the constrained analogue 9 displayed potent mu-agonist activity in vitro. This study provides additional information about the molecular determinants for mu recognition, the structural features affecting ligand binding, and the structure function relationships.

  DOI：

  10.1021/jm060486f

文献信息

• Elucidation of the Bioactive Conformation of the <i>N</i>-Substituted <i>trans</i>-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Class of μ-Opioid Receptor Antagonists
  作者：Bertrand Le Bourdonnec、Allan J. Goodman、Mathieu Michaut、Hai-Fen Ye、Thomas M. Graczyk、Serge Belanger、Torsten Herbertz、Glenn P. A. Yap、Robert N. DeHaven、Roland E. Dolle

  DOI：10.1021/jm060486f

  日期：2006.12.1

  The series of trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidines have been widely investigated as opioid receptor antagonists. One of our research goals was to explore the bioactive conformation of the N-phenethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine derivative 3, prototypical A-opioid antagonist in this series. In this effort, the rotational degrees of freedom of the N-substituent of 3 were limited by incorporation of an ethylene bridge between the piperidine 2- or 6-position of 3 and the benzylic position of the N-phenethyl moiety. The overall modification led to a novel series of fused bicyclic derivatives of the octahydroquinolizine chemical class, conformationally restricted analogue of 3. The constrained analogues 6 and 9 showed high affinity toward the mu-opioid receptor. Compound 6 was found to be a mu-opioid antagonist, whereas the constrained analogue 9 displayed potent mu-agonist activity in vitro. This study provides additional information about the molecular determinants for mu recognition, the structural features affecting ligand binding, and the structure function relationships.