(2R,4R,5R)-2-allyl-4-(3-(benzyloxy)phenyl)-4,5-dimethyl-piperidine | 918423-39-9

• 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: (2R,4R,5R)-2-allyl-4-(3-(benzyloxy)phenyl)-4,5-dimethyl-piperidine
• 英文别名: (2R,4R,5R)-4,5-dimethyl-4-(3-phenylmethoxyphenyl)-2-prop-2-enylpiperidine
• CAS: 918423-39-9
• 化学式: C₂₃H₂₉NO
• 分子量: 335.489
• InChiKey: ZLLAZIXMJAHSEY-QTGUNEKASA-N

物化性质

• 沸点：
  458.3±45.0 °C(Predicted)
• 密度：
  0.989±0.06 g/cm3(Predicted)

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：

  (2R,4R,5R)-2-allyl-4-(3-(benzyloxy)phenyl)-4,5-dimethyl-piperidine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium on activated charcoal dimethyl sulfide borane 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 3-((2R,3R,9αR)-2,3-dimethyl-octahydro-1H-quinolizin-2-yl)phenol
  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 为溶剂， 生成 (2R,4R,5R)-2-allyl-4-(3-(benzyloxy)phenyl)-4,5-dimethyl-piperidine
  参考文献：
  名称：

  一系列新的2α-取代的反式-4,5-二甲基-4-（3-羟苯基）哌啶作为mu选择性阿片类拮抗剂的合成与构效关系。

  摘要：

  研究了反式-4,5-二甲基-4-（3-羟苯基）哌啶mu-阿片样物质拮抗剂系列的哌啶环的2α-位的构效关系。这项研究表明，在该系列哌啶环的2α-位仅能容忍小的直链烷基（甲基，丙基）。

  DOI：

  10.1016/j.bmcl.2005.11.010

文献信息

• Synthesis and structure–activity relationships of a new series of 2α-substituted trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine as μ-selective opioid antagonists
  作者：Bertrand Le Bourdonnec、Allan J. Goodman、Mathieu Michaut、Hai-Fen Ye、Thomas M. Graczyk、Serge Belanger、Robert N. DeHaven、Roland E. Dolle

  DOI：10.1016/j.bmcl.2005.11.010

  日期：2006.2

  Structure-activity relationships at the 2alpha-position of the piperidine ring of the trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine mu-opioid antagonist series were investigated. This study showed that only small linear alkyl groups (methyl, propyl) are tolerated at the 2alpha-position of the piperidine ring of this series.

  研究了反式-4,5-二甲基-4-（3-羟苯基）哌啶mu-阿片样物质拮抗剂系列的哌啶环的2α-位的构效关系。这项研究表明，在该系列哌啶环的2α-位仅能容忍小的直链烷基（甲基，丙基）。
• 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.