(-)-N-benzyloxymorphone | 503091-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (-)-N-benzyloxymorphone
• 英文别名: (4R,4aS,7aR,12bS)-3-benzyl-4a,9-dihydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 503091-10-9
• 化学式: C₂₃H₂₃NO₄
• 分子量: 377.44
• InChiKey: BQBZWCBDBSMPNH-HGSOSGBHSA-N

物化性质

• 沸点：
  590.7±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  14-羟基二氢降吗啡酮盐酸盐 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (-)-N-benzyloxymorphone
  参考文献：
  名称：

  Opioids and efflux transporters. Part 4: Influence of N-substitution on P-glycoprotein substrate activity of noroxymorphone analogues

  摘要：

  The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demonstrated to be up-regulated in rats tolerant to morphine and oxycodone. We have previously examined the influence of hydrogen-bonding oxo-substitutents on the P-gp-mediated efflux of 4,5-epoxymorphinan analgesics, as well as that of N-substituted analogues of meperidine. Structure activity relationships (SAR) governing N-substituent effects on opioid efficacy is well-established, however the influence of such structural modifications on P-gp-mediated efflux is unknown. Here, we present SAR describing P-gp recognition of a short series of N-modified 4,5-epoxymorphinans. Oxymorphone, naloxone, naltrexone, and nalmexone all failed to demonstrate P-gp substrate activity, indicating these opioid scaffolds contain structural features that preclude recognition by the transporter. These results are examined using mathematical molecular modeling and discussed in comparison to other opioid scaffolds bearing similar N-substituents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.033

文献信息

• Processes for the selective amination of ketomorphinans
  申请人：Hudson Edumnd C.

  公开号：US20100081817A1

  公开（公告）日：2010-04-01

  The present invention is generally directed to a process for the preparation of a ketomorphinan comprising maintaining a ketone group as unprotected and performing reductive amination using a hydrogen source and a catalyst.

  本发明通常涉及一种制备酮吗啡类化合物的过程，其中保持酮基未保护，并使用氢源和催化剂进行还原胺化反应。
• US8269006B2
  申请人：——

  公开号：US8269006B2

  公开（公告）日：2012-09-18
• Opioids and efflux transporters. Part 4: Influence of N-substitution on P-glycoprotein substrate activity of noroxymorphone analogues
  作者：Matthew D. Metcalf、Andrew D. Rosicky、Hazem E. Hassan、Natalie D. Eddington、Andrew Coop、Christopher W. Cunningham、Susan L. Mercer

  DOI：10.1016/j.bmcl.2014.05.033

  日期：2014.8

  The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demonstrated to be up-regulated in rats tolerant to morphine and oxycodone. We have previously examined the influence of hydrogen-bonding oxo-substitutents on the P-gp-mediated efflux of 4,5-epoxymorphinan analgesics, as well as that of N-substituted analogues of meperidine. Structure activity relationships (SAR) governing N-substituent effects on opioid efficacy is well-established, however the influence of such structural modifications on P-gp-mediated efflux is unknown. Here, we present SAR describing P-gp recognition of a short series of N-modified 4,5-epoxymorphinans. Oxymorphone, naloxone, naltrexone, and nalmexone all failed to demonstrate P-gp substrate activity, indicating these opioid scaffolds contain structural features that preclude recognition by the transporter. These results are examined using mathematical molecular modeling and discussed in comparison to other opioid scaffolds bearing similar N-substituents. (C) 2014 Elsevier Ltd. All rights reserved.