N-(2-methylallyl)oxymorphone | 384820-54-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: N-(2-methylallyl)oxymorphone
• 英文别名: (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-(2-methylprop-2-enyl)-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 384820-54-6
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: JOSIFEYTJBIMBI-XFWGSAIBSA-N

物化性质

• 沸点：
  540.0±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-methylallyl)oxymorphone 在 12-冠醚-4 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 51.0h， 生成 (4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-(2-methylprop-2-enyl)spiro[1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6,2'-1,3-dihydroindene]-7-one
  参考文献：
  名称：

  Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: variation of the delta address and its effects on affinity and selectivity for the delta opioid receptor

  摘要：

  In an effort to establish the importance of the N-(2-methylallyl) substituent in the noroxymorphone series, several derivatives have been synthesized, retaining that N-substituent and modifying the delta address moiety. A few compounds showed moderate binding affinity and selectivity for the delta receptor; none displayed a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole, A second study showed that 3-O-methylation of all derivatives decreases binding affinity. The present results indicate that only a combination of the N-(2-methylallyl) group and an indole delta address provided high selectivity for the delta receptor. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00580-7
• 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-(2-methylallyl)oxymorphone
  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

• Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: variation of the delta address and its effects on affinity and selectivity for the delta opioid receptor
  作者：Thomas Ullrich、Christina M Dersch、Richard B Rothman、Arthur E Jacobson、Kenner C Rice

  DOI：10.1016/s0960-894x(01)00580-7

  日期：2001.11

  In an effort to establish the importance of the N-(2-methylallyl) substituent in the noroxymorphone series, several derivatives have been synthesized, retaining that N-substituent and modifying the delta address moiety. A few compounds showed moderate binding affinity and selectivity for the delta receptor; none displayed a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole, A second study showed that 3-O-methylation of all derivatives decreases binding affinity. The present results indicate that only a combination of the N-(2-methylallyl) group and an indole delta address provided high selectivity for the delta receptor. Published by Elsevier Science Ltd.
• 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.