3-(2-bromoethyl)-5-(3-methoxyphenyl)-8,9-dimethyl-2-oxa-8-azabicyclo[3.3.1]nonane | 873313-71-4

• 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: 3-(2-bromoethyl)-5-(3-methoxyphenyl)-8,9-dimethyl-2-oxa-8-azabicyclo[3.3.1]nonane
• 英文别名: 3-(2-Bromoethyl)-5-(3-methoxyphenyl)-8,9-dimethyl-2-oxa-8-azabicyclo[3.3.1]nonane
• CAS: 873313-71-4
• 化学式: C₁₈H₂₆BrNO₂
• 分子量: 368.314
• InChiKey: GNFHQUXZKKJWGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-bromoethyl)-5-(3-methoxyphenyl)-8,9-dimethyl-2-oxa-8-azabicyclo[3.3.1]nonane 在 草酰氯 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 40.0h， 生成 N-methyl-4a-(3-methoxyphenyl)-8a-methyl-6-oxooctahydroisoquinoline
  参考文献：
  名称：

  N-Substituted cis-4a-(3-Hydroxyphenyl)-8a-methyloctahydroisoquinolines Are Opioid Receptor Pure Antagonists

  摘要：

  N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctabydroisoquinolines 6a-g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial, similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single-crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has lower potential energy relative to that of the axial conformation. Evaluation of 6a-g in the [S-35]GTP-gamma-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a K-e of 0.27 nM at the kappa opioid receptor with 154- and 46-fold selectivity relative to those of the mu and 6 receptors, respectively, possessed the best combination Of K potency and selectivity.

  DOI：

  10.1021/jm058261c
• 作为产物：
  描述：

  5-(3-methoxyphenyl)-8,9-dimethyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]methyl-2-oxa-8-azabicyclo[3.3.1]nonane 在 溴 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到3-(2-bromoethyl)-5-(3-methoxyphenyl)-8,9-dimethyl-2-oxa-8-azabicyclo[3.3.1]nonane
  参考文献：
  名称：

  N-Substituted cis-4a-(3-Hydroxyphenyl)-8a-methyloctahydroisoquinolines Are Opioid Receptor Pure Antagonists

  摘要：

  N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctabydroisoquinolines 6a-g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial, similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single-crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has lower potential energy relative to that of the axial conformation. Evaluation of 6a-g in the [S-35]GTP-gamma-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a K-e of 0.27 nM at the kappa opioid receptor with 154- and 46-fold selectivity relative to those of the mu and 6 receptors, respectively, possessed the best combination Of K potency and selectivity.

  DOI：

  10.1021/jm058261c

文献信息

• Octahydroisoquinoline compounds as opioid receptor modulators
  申请人：Carroll Ivy Frank

  公开号：US20070027182A1

  公开（公告）日：2007-02-01

  Compounds which bind to opioid receptors are provided. In a preferred embodiment of the invention, the compounds are opioid receptor antagonists. The present invention also provides methods of treating conditions which are mediated by an opioid receptor.

  提供结合到阿片受体的化合物。在发明的首选实施例中，这些化合物是阿片受体拮抗剂。本发明还提供了治疗由阿片受体介导的疾病的方法。
• US7476679B2
  申请人：——

  公开号：US7476679B2

  公开（公告）日：2009-01-13
• N-Substituted <i>cis-</i>4a-(3-Hydroxyphenyl)-8a-methyloctahydroisoquinolines Are Opioid Receptor Pure Antagonists
  作者：F. Ivy Carroll、Sachin Chaudhari、James B. Thomas、S. Wayne Mascarella、Kenneth M. Gigstad、Jeffrey Deschamps、Hernán A. Navarro

  DOI：10.1021/jm058261c

  日期：2005.12.1

  N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctabydroisoquinolines 6a-g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial, similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single-crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has lower potential energy relative to that of the axial conformation. Evaluation of 6a-g in the [S-35]GTP-gamma-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a K-e of 0.27 nM at the kappa opioid receptor with 154- and 46-fold selectivity relative to those of the mu and 6 receptors, respectively, possessed the best combination Of K potency and selectivity.