4,5-epoxy-3-methoxy-17-methyl-morphinan-6-ol | 125-28-0

• 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: 4,5-epoxy-3-methoxy-17-methyl-morphinan-6-ol
• 英文别名: Dihydrocodein-Base；Dihydro-isocodein；Dihydroisocodein；Dihydrothebainol；Dihydrocodeinon；Dihydrocodeinum；Dihydroneopine；9-methoxy-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
• CAS: 125-28-0；795-38-0；28379-49-9；29699-74-9；144408-29-7
• 化学式: C₁₈H₂₃NO₃
• 分子量: 301.386
• InChiKey: RBOXVHNMENFORY-UHFFFAOYSA-N

物化性质

• 熔点：
  199-200°
• 溶解度：
  可溶于氯仿（轻微，超声处理）、DMSO（轻微）、乙酸乙酯（轻微）
• 保留指数：
  2357;2357;2323;2365;2376;2350;2363;2371.8;2405.5;2365;2335;2375;2363

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期间使用概要：哺乳期母亲口服麻醉剂可能会导致婴儿昏昏欲睡，严重的中枢神经系统抑制。与可待因类似，药物遗传学可能在中枢神经系统抑制的程度中发挥作用。新生儿似乎对即使是小剂量的麻醉性镇痛剂的影响也非常敏感。在一项研究中，双氢可待因可能导致了接受该药物治疗咳嗽的母亲的新生儿严重呼吸抑制。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，并将母亲的氢吗啡酮摄入量限制在2到3天，剂量较低，并且密切监测婴儿。如果婴儿表现出过度嗜睡（比平时更甚）、哺乳困难、呼吸问题或无力，应立即联系医生。由于关于哺乳期间使用双氢可待因的已发表经验很少，可能更倾向于选择另一种药物，特别是在哺乳新生儿或早产儿时。 ◉ 对哺乳婴儿的影响：一名妇女从分娩后第一天开始，每天两次服用双氢可待因滴剂（5.28毫克）治疗咳嗽。一天后，她的哺乳婴儿难以唤醒，并且哺乳情况不佳。婴儿出现了心动过缓、低血糖和血氧饱和度为85%。在医院住了24小时后，所有症状都得到了解决。这些症状可能是由乳汁中的双氢可待因引起的。 ◉ 对泌乳和母乳的影响：麻醉剂可以增加血清催乳素水平。然而，对于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:Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Like codeine, pharmacogenetics probably plays a role in the extent of central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Dihydrocodeine possibly caused severe respiratory depression in one newborn infant whose mother was taking the drug for cough. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of hydromorphone to 2 to 3 days at a low dosage 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. Because there is little published experience with dihydrocodeine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants:A woman began taking dihydrocodeine drops for cough twice daily (5.28 mg) beginning on the first day postpartum. One day later, her breastfed infant was difficult to arouse and was not breastfeeding well. The infant had bradycardia, hypoglycemia, and an oxygen saturation of 85%. After 24 hours in the hospital, all symptoms resolved. The symptoms were possibly caused by dihydrocodeine in milk. ◉ 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)

安全信息

• 海关编码：
  2939110012

文献信息

• [EN] STEPWISE PROCESS FOR THE PRODUCTION OF ALKALOID SALTS<br/>[FR] PROCÉDÉ PAR ÉTAPES POUR OBTENTION DE SELS D'ALCALOÏDES
  申请人：MALLINCKRODT LLC

  公开号：WO2013019825A1

  公开（公告）日：2013-02-07

  The present Invention provides to an improved process for preparing alkaloid salts. In particular, the process comprises a stepwise addition of an acid to an alkaloid chosen from hydrocodone, codeine, and dihydrocodeine to form a flowable mixture of the alkaloid salt

  本发明提供了一种改进的制备生物碱盐的方法。具体而言，该方法包括逐步向羟考酮、可待因和二氢可待因中选择的生物碱添加酸，以形成生物碱盐的可流动混合物。
• One Pot Process for Producing 6-Hydroxyl Nal-Opiate
  申请人：Mallinckrodt LLC

  公开号：US20130203999A1

  公开（公告）日：2013-08-08

  The present invention provides processes for preparing nal-opiates without the isolation of intermediates. In general, the process provides for alkylation and reduction in the same pot to give the nal-opiate.

  本发明提供了一种制备纳洛酮类药物的方法，无需分离中间体。一般来说，该方法在同一容器中进行烷基化和还原反应，从而得到纳洛酮类药物。
• 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。
• Process for the Preparation of 6-Beta Hydroxy Morphinan Compounds
  申请人：Bao Jian

  公开号：US20090312552A1

  公开（公告）日：2009-12-17

  The invention provides processes for the conversion of a 6-keto morphinan to a 6-hydroxy morphinan. In particular, the invention provides a stereoselective process for the conversion of a 6-keto morphinan to a 6-beta-hydroxy morphinan.

  该发明提供了将6-酮吗啡烷转化为6-羟基吗啡烷的过程。具体地，该发明提供了一种立体选择性的过程，用于将6-酮吗啡烷转化为6-β-羟基吗啡烷。
• 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