(+)-oxymorphone

• 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: (+)-oxymorphone
• 英文别名: 3,14-Dihydroxy-17-methyl-4,5-epoxymorphinan-6-one；4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.342
• InChiKey: UQCNKQCJZOAFTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

代谢

Oxymorphone 是已知的氧化可待因的人类代谢物。

Oxymorphone is a known human metabolite of oxycodone.

来源:NORMAN Suspect List Exchange

毒理性

• 在妊娠和哺乳期间的影响

母乳喂养期间的使用总结：目前没有关于在哺乳期间使用氧吗啡的数据。哺乳期母亲使用口服麻醉剂可能会导致婴儿昏睡，严重的中枢神经系统抑制。新生儿似乎对即使是小剂量的麻醉性镇痛剂的作用也非常敏感。一旦母亲的乳汁开始分泌，最好使用非麻醉性镇痛剂来控制疼痛，并限制母亲在2到3天内低剂量口服氧吗啡，同时密切监测婴儿。如果婴儿表现出过度嗜睡（比平时更甚）、哺乳困难、呼吸困难或软弱无力，应立即联系医生。在哺乳期间，首选其他药物而不是氧吗啡。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：麻醉剂可以提高血清催乳素水平。然而，对于一个已经建立泌乳的母亲来说，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:No data are available on the use of oxymorphone during breastfeeding. Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral oxymorphone for 2 to 3 days at low dosages, with close infant monitoring. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Other agents are preferred over oxymorphone during breastfeeding. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Narcotics can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  (+)-oxymorphone 在 ammonium acetate 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N,N'-bis[2-[[2-[(4a,9-dihydroxy-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino]-2-oxoethyl]amino]-2-oxoethyl]butanediamide
  参考文献：
  名称：

  阿片激动剂和拮抗剂二价配体的立体构效关系。在邻近阿片受体之间桥接的证据。

  摘要：

  DOI：

  10.1021/jm00147a002

文献信息

• Novel Therapeutic Compounds
  申请人：SESHA Ramesh

  公开号：US20120046272A1

  公开（公告）日：2012-02-23

  The present invention describes a series of therapeutically active compounds of formula I, X—Y—Z  (I) that are useful for treating a disorder in a mammal. In the formula I, X and Z, which may be same or different, are independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group or substituted or unsubstituted heterocyclylalkyl; and Y is a linker selected from —O—, —S—, —NH—, —(CH 2 ) n —, —CO—, —CONR a —, —NR a CO—, —NR a COO—, —COO—, —CONR a CO—, —CONR a COO— and —COOCOO—. The compounds are useful to treat neurodegenerative disorders, depression, Alzheimer's disease, cognitive disorders, motor disorders, Parkinson's disease, drug addiction, behavioral disorders, inflammatory disorders, stomach disorders, cancers, acute pain, chronic pain and recurrent pain.

  本发明描述了一系列具有治疗活性的化合物，其化学式为I，X—Y—Z  (I)，适用于治疗哺乳动物中的某种疾病。在化学式I中，X和Z，可以相同也可以不同，独立地选择自取代或未取代的烷基、取代或未取代的烯基、取代或未取代的环烷基、取代或未取代的环烷基烷基、取代或未取代的芳基、取代或未取代的芳基烷基、取代或未取代的杂芳基、取代或未取代的杂芳基烷基、取代或未取代的杂环基团或取代或未取代的杂环烷基；Y是从—O—、—S—、—NH—、—(CH2)n—、—CO—、—CONRa—、—NRaCO—、—NRaCOO—、—COO—、—CONRaCO—、—CONRaCOO—和—COOCOO—中选择的连接基团。这些化合物适用于治疗神经退行性疾病、抑郁症、阿尔茨海默病、认知障碍、运动障碍、帕金森病、药物成瘾、行为障碍、炎症性疾病、胃病、癌症、急性疼痛、慢性疼痛和复发性疼痛。
• Preparation of 6-Alpha-Amino N-Substituted Morphinans by Catalytic Hydrogen Transfer
  申请人：Grote Christopher W.

  公开号：US20100317683A1

  公开（公告）日：2010-12-16

  The present invention provides processes for the stereoselective synthesis of 6-alpha-amino N-substituted morphinans. In particular, the invention provides processes for the reductive amination of 6-keto N-substituted morphinans by catalytic hydrogen transfer.

  本发明提供了用于立体选择性合成6-α-氨基N-取代吗啡酮类化合物的方法。具体来说，该发明提供了通过催化氢转移的还原胺化反应合成6-酮N-取代吗啡酮类化合物的方法。
• Processes for the preparation of normorphinan salts
  申请人：Wang Peter X.

  公开号：US20090156819A1

  公开（公告）日：2009-06-18

  The invention provides a process for the conversion of opioid derivatives into normorphinan compounds useful for making “nal” compound analgesics and antagonists. In particular, the process may be used for the production of pure normorphinan salts from crude opioid substrates.

  本发明提供了一种将阿片类衍生物转化为正吗啡烷类化合物的方法，该方法可用于制备“nal”化合物镇痛剂和拮抗剂。特别地，该方法可用于从粗制阿片类底物中生产纯正吗啡烷盐。
• [EN] PREPARATION OF 6-ALPHA-AMINO N-SUBSTITUTED MORPHINANS BY CATALYTIC HYDROGEN TRANSFER<br/>[FR] PRÉPARATION DE MORPHINANES 6-ALPHA-AMINO N-SUBSTITUÉS PAR TRANSFERT CATALYTIQUE D'HYDROGÈNE
  申请人：MALLINCKRODT INC

  公开号：WO2010144641A1

  公开（公告）日：2010-12-16

  The present invention provides processes for the stereoselective synthesis of 6-alpha-amino N-substituted morphinans. In particular, the invention provides processes for the reductive amination of 6-keto N-substituted morphinans by catalytic hydrogen transfer.

  本发明提供了用于立体选择性合成6-α-氨基N-取代吗啡烷的过程。特别地，本发明提供了通过催化氢转移还原胺化6-酮基N-取代吗啡烷的过程。
• Multi-arm polymer prodrugs
  申请人：Zhao Xuan

  公开号：US20080194612A1

  公开（公告）日：2008-08-14

  Provided herein are water-soluble prodrugs. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

  本文提供了一种水溶性的前药。该发明的前药包括一个水溶性聚合物，具有三个或更多的臂，其中至少三个臂与活性剂（例如小分子）共价连接。本发明的结合物提供了聚合物大小和结构的最佳平衡，以实现改善药物负载，因为本发明的结合物具有三个或更多的活性剂可释放地连接到多臂水溶性聚合物上。本发明的前药具有治疗效果，并在体内表现出比未修改的母体药物更好的性能。

表征谱图