(3R,7R,8R,9aS)-8-(3-hydroxyphenyl)-7,8-dimethyl-3-phenyl-hexahydro-1H-quinolizin-4(6H)-one | 918423-50-4

• 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,7R,8R,9aS)-8-(3-hydroxyphenyl)-7,8-dimethyl-3-phenyl-hexahydro-1H-quinolizin-4(6H)-one
• 英文别名: (3R,7R,8R,9aS)-8-(3-hydroxyphenyl)-7,8-dimethyl-3-phenyl-2,3,6,7,9,9a-hexahydro-1H-quinolizin-4-one
• CAS: 918423-50-4
• 化学式: C₂₃H₂₇NO₂
• 分子量: 349.473
• InChiKey: FBTQLQLUYCHWJQ-PZMSFCMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,7R,8R,9aS)-8-(3-hydroxyphenyl)-7,8-dimethyl-3-phenyl-hexahydro-1H-quinolizin-4(6H)-one 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 以78%的产率得到3-[(2R,3R,7R,9aS)-2,3-dimethyl-7-phenyl-1,3,4,6,7,8,9,9a-octahydroquinolizin-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：

  1-((2S,4R,5R)-2-allyl-4-(3-(benzyloxy)phenyl)-4,5-dimethyl-piperidin-1-yl)-2-phenylethane-1,2-dione 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium on activated charcoal potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 (3R,7R,8R,9aS)-8-(3-hydroxyphenyl)-7,8-dimethyl-3-phenyl-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

文献信息

• NOVEL OPIOID ANTAGONISTS
  申请人：Dolle E. Roland

  公开号：US20070105863A1

  公开（公告）日：2007-05-10

  Certain quinolizidine and octahydropyridopyrazine compounds, pharmaceutical compositions, and methods of their use, inter alia, as opioid receptor antagonists are disclosed.

  某些喹诺里西啶和八氢吡啶吡嗪化合物、药物组合物及其使用方法被披露，例如作为阿片受体拮抗剂。
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