(7R,8R,9aS)-8-(3-(benzyloxy)phenyl)-7,8-dimethyl-7,8,9,9a-tetrahydro-1H-quinolizin-4(6H)-one | 918423-56-0

• 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: (7R,8R,9aS)-8-(3-(benzyloxy)phenyl)-7,8-dimethyl-7,8,9,9a-tetrahydro-1H-quinolizin-4(6H)-one
• 英文别名: (7R,8R,9aS)-7,8-dimethyl-8-(3-phenylmethoxyphenyl)-6,7,9,9a-tetrahydro-1H-quinolizin-4-one
• CAS: 918423-56-0
• 化学式: C₂₄H₂₇NO₂
• 分子量: 361.484
• InChiKey: BXWHWRCGQROVAX-NSXLHWASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (7R,8R,9aS)-8-(3-(benzyloxy)phenyl)-7,8-dimethyl-7,8,9,9a-tetrahydro-1H-quinolizin-4(6H)-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以100%的产率得到(7R,8R,9aS)-8-(3-hydroxyphenyl)-7,8-dimethyl-hexahydro-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 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) sodium tungstate 、 双氧水 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 19.5h， 生成 (7R,8R,9aS)-8-(3-(benzyloxy)phenyl)-7,8-dimethyl-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

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.