7α-spirobenzocyclohexylhydrocodone | 194468-69-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 7α-spirobenzocyclohexylhydrocodone
• 英文别名: (4R,4aR,6R,7aR,12bS)-9-methoxy-3-methylspiro[2,4,4a,5,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-6,3'-2,4-dihydro-1H-naphthalene]-7-one
• CAS: 194468-69-4
• 化学式: C₂₇H₂₉NO₃
• 分子量: 415.532
• InChiKey: SKAUVVUQZYSFQA-UURBWOCOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7α-spirobenzocyclohexylhydrocodone 在 三溴化硼 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 以42%的产率得到7α-spirobenzocyclohexylhydromorphone
  参考文献：
  名称：

  7-Spirobenzocyclohexyl Derivatives of Naltrexone, Oxymorphone, and Hydromorphone as Selective Opioid Receptor Ligands

  摘要：

  On the basis of previous structure-activity studies of the highly potent and selective delta-opioid receptor antagonist naltrindole (1) and the spiroindanyl anologues 2 and 3, we have synthesized epimeric pairs of spirobenzocyclohexyl derivatives of naltrexone, oxymorphone, and hydromorphone (4-9). Pharmacologic evaluation in smooth muscle assays has revealed that the oxymorphone derivatives (6, 7) are delta-selective agonists and possess receptor binding profiles that are consistent with their agonist activity. It is proposed that the spirobenzocyclohexyl group of 6 and 7 orients its benzene moiety orthogonally with respect to the C ring of the opiate in a manner similar to that of the spiroindanyl analogue 3. It is suggested that this orthogonal orientation serves as an ''address'' to facilitate activation of delta receptors. The finding that the hydromorphone analogues (8, 9) were full mu agonists and exhibited only partial delta agonist activity suggests that the 14-hydroxyl group also contributes to the delta agonist activity. The naltrexone derivatives (4, 5) were mu-selective antagonists and exhibited relatively weak delta antagonist activity. However, the binding data indicated a very high-affinity delta-selective binding profile that was not consistent with the pharmacology. This study illustrates the differential contributions of the delta ''address'' to agonist and antagonist activity and supports the idea of different recognition sites for interaction of agonist and antagonist ligands with delta-opioid receptors.

  DOI：

  10.1021/jm970283e
• 作为产物：
  描述：

  邻羧基苯乙酸 在 lithium aluminium tetrahydride 、 12-冠醚-4 、 四溴化碳 、 三苯基膦 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 59.25h， 生成 7α-spirobenzocyclohexylhydrocodone
  参考文献：
  名称：

  7-Spirobenzocyclohexyl Derivatives of Naltrexone, Oxymorphone, and Hydromorphone as Selective Opioid Receptor Ligands

  摘要：

  On the basis of previous structure-activity studies of the highly potent and selective delta-opioid receptor antagonist naltrindole (1) and the spiroindanyl anologues 2 and 3, we have synthesized epimeric pairs of spirobenzocyclohexyl derivatives of naltrexone, oxymorphone, and hydromorphone (4-9). Pharmacologic evaluation in smooth muscle assays has revealed that the oxymorphone derivatives (6, 7) are delta-selective agonists and possess receptor binding profiles that are consistent with their agonist activity. It is proposed that the spirobenzocyclohexyl group of 6 and 7 orients its benzene moiety orthogonally with respect to the C ring of the opiate in a manner similar to that of the spiroindanyl analogue 3. It is suggested that this orthogonal orientation serves as an ''address'' to facilitate activation of delta receptors. The finding that the hydromorphone analogues (8, 9) were full mu agonists and exhibited only partial delta agonist activity suggests that the 14-hydroxyl group also contributes to the delta agonist activity. The naltrexone derivatives (4, 5) were mu-selective antagonists and exhibited relatively weak delta antagonist activity. However, the binding data indicated a very high-affinity delta-selective binding profile that was not consistent with the pharmacology. This study illustrates the differential contributions of the delta ''address'' to agonist and antagonist activity and supports the idea of different recognition sites for interaction of agonist and antagonist ligands with delta-opioid receptors.

  DOI：

  10.1021/jm970283e

文献信息

• 7-Spirobenzocyclohexyl Derivatives of Naltrexone, Oxymorphone, and Hydromorphone as Selective Opioid Receptor Ligands
  作者：Xinqin Fang、Dennis L. Larson、Philip S. Portoghese

  DOI：10.1021/jm970283e

  日期：1997.9.1

  On the basis of previous structure-activity studies of the highly potent and selective delta-opioid receptor antagonist naltrindole (1) and the spiroindanyl anologues 2 and 3, we have synthesized epimeric pairs of spirobenzocyclohexyl derivatives of naltrexone, oxymorphone, and hydromorphone (4-9). Pharmacologic evaluation in smooth muscle assays has revealed that the oxymorphone derivatives (6, 7) are delta-selective agonists and possess receptor binding profiles that are consistent with their agonist activity. It is proposed that the spirobenzocyclohexyl group of 6 and 7 orients its benzene moiety orthogonally with respect to the C ring of the opiate in a manner similar to that of the spiroindanyl analogue 3. It is suggested that this orthogonal orientation serves as an ''address'' to facilitate activation of delta receptors. The finding that the hydromorphone analogues (8, 9) were full mu agonists and exhibited only partial delta agonist activity suggests that the 14-hydroxyl group also contributes to the delta agonist activity. The naltrexone derivatives (4, 5) were mu-selective antagonists and exhibited relatively weak delta antagonist activity. However, the binding data indicated a very high-affinity delta-selective binding profile that was not consistent with the pharmacology. This study illustrates the differential contributions of the delta ''address'' to agonist and antagonist activity and supports the idea of different recognition sites for interaction of agonist and antagonist ligands with delta-opioid receptors.