hydrocodone | 1082738-67-7

• 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: hydrocodone
• 英文别名: Dihydrocodeinon；Hydrocodon；Dicodid；9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 1082738-67-7
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: LLPOLZWFYMWNKH-UHFFFAOYSA-N

物化性质

• 沸点：
  461.4±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)
• 保留指数：
  2401;2411;2441.6;2424.6;2452.2;2390;2440

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：
  0.61
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：氢可酮是一种阿片类麻醉药。苯氢可酮是一种氢可酮的前药，在胃肠系统中迅速转化为氢可酮。哺乳期母亲口服麻醉药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很小的麻醉性镇痛药剂量都非常敏感。一旦母亲的乳汁开始分泌，最好使用非麻醉性镇痛药来控制疼痛，并限制母亲口服氢可酮的时间为2到3天，最大剂量每天30毫克，并密切监测婴儿。如果婴儿表现出过度昏睡（比平常更甚）、哺乳困难、呼吸问题或无力，应立即联系医生。 ◉ 对哺乳婴儿的影响：一名正在哺乳的母亲服用20毫克口服氢可酮，并每隔4小时与1300毫克扑热息痛（对乙酰氨基酚）联合使用，治疗疼痛的乳头念珠菌病和乳腺炎，她的18天大的婴儿变得昏昏欲睡并“一整天大部分时间都在睡觉”。母亲将剂量减少了一半，婴儿似乎不再经历昏昏欲睡或过度嗜睡。婴儿的症状可能是由母亲的氢可酮引起的。 一名5周大的哺乳婴儿变得发绀并需要口对口人工呼吸和插管。婴儿的尿液中检测到阿片类药物呈阳性，并对纳洛酮有积极反应；意识水平在2天内有所改善并成功拔管。婴儿的母亲承认在哺乳前服用了氢可酮-扑热息痛复方制剂和甲基吗啡（美沙酮），这些药物是为偏头痛头痛而开的处方。婴儿的症状可能是由母亲的阿片类药物使用引起的。 ◉ 对泌乳和母乳的影响：麻醉药可以增加血清催乳素。然而，对于已经建立泌乳的母亲，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Hydrocodone is an opioid narcotic. Benzhydrocodone is a hydrocodone prodrug that is rapidly converted into hydrocodone in the gastrointestinal tract. 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 hydrocodone to 2 to 3 days at a maximum dosage of 30 mg daily 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. ◉ Effects in Breastfed Infants:The 18-day-old infant of a breastfeeding mother became groggy and "slept for most of the day" while the mother was taking 20 mg of oral hydrocodone combined with 1300 mg of acetaminophen every 4 hours for painful nipple candidiasis and mastitis. The mother decreased her dose by one-half and the infant apparently no longer experienced grogginess or hypersomnolence. The infant's symptoms were probably due to the maternal hydrocodone. A 5-week-old breastfed infant became cyanotic and required mouth-to-mouth resuscitation and intubation. The infant's urine was positive for opioids and the infant responded positively to naloxone; the level of consciousness improved over 2 days and extubation was accomplished. The infant's mother admitted to taking a hydrocodone-acetaminophen combination product and methadone that had been prescribed for migraine headache before she was breastfeeding. The infant's symptoms were probably due to the maternal opiate use. ◉ 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：

  hydrocodone 、 sodium ethanolate 、 6-氨基苯并[1,3]二氧杂环戊烯-5-甲醛 生成 alkaline earth salt of/the/ methylsulfuric acid
  参考文献：
  名称：

  Gulland, Journal of the Chemical Society, 1928, p. 703

  摘要：

  DOI：
• 作为产物：
  描述：

  可待因 在 环己酮 、 镍 、 甲苯 作用下， 生成 hydrocodone
  参考文献：
  名称：

  The Preparation and Degradation of 6-Methylcodeine¹

  摘要：

  DOI：

  10.1021/ja01163a127

文献信息

• Heterogeneous Ruthenium Metal Catalyst for the Production of Hydrocodone, Hydromorphone or a Derivative Thereof
  申请人：GINDELBERGER David E.

  公开号：US20110071016A1

  公开（公告）日：2011-03-24

  The present disclosure generally relates to catalytic methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydrocodone, hydromorphone, or a derivative thereof, by means of a conversion or an isomerization of codeine, morphine, or a derivative thereof, respectively, using a heterogeneous ruthenium metal catalyst.

  本公开涉及一般用于生产阿片类衍生物的催化方法。更具体地，本公开涉及通过使用异质钌金属催化剂，通过对可待因、吗啡或其衍生物进行转化或异构化的方式，制备羟考酮、羟吗啡或其衍生物。
• 6-monoacetylmorphine derivatives useful in immunoassay
  申请人：Roche Diagnostics GmbH

  公开号：EP1810973A1

  公开（公告）日：2007-07-25

  Analogs of 6-monoacetyl morphine (6-MAM) are described. These include analogs derivatized at either the C-3 position, the C-6 position, or the nor position of the molecule. These analogs allow for elaboration with linkers terminated by a functional group such as an activated ester, the functional groups being useful for attaching the molecule to other entities such as proteins, polysaccharides, and reporter groups.

  6-单乙酰吗啡（6-MAM）的类似物被描述。这些包括在分子的C-3位置、C-6位置或去甲位置进行衍生的类似物。这些类似物允许通过以活化酯等功能团终止的连接剂进行扩展，这些功能团对于将分子附着到其他实体（如蛋白质、多糖和报告基团）非常有用。
• BENZOIC ACID, BENZOIC ACID DERIVATIVES AND HETEROARYL CARBOXYLIC ACID CONJUGATES OF HYDROCODONE, PRODRUGS, METHODS OF MAKING AND USE THEREOF
  申请人：Mickle Travis

  公开号：US20110002990A1

  公开（公告）日：2011-01-06

  The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

  目前描述的技术提供了包含芳基羧酸与羟考酮（吗啡酮-6-酮，4,5-α-环氧-3-甲氧基-17-甲基）化学共轭形成的新型羟考酮前药/组合物，包括苯甲酸酯和杂环芳基羧酸，具有降低滥用羟考酮潜力的特性。该技术还提供了治疗患者的方法、制药工具包和合成本技术共轭物的方法。
• Methods for Producing Hydrocodone, Hydromorphone or a Derivative Thereof
  申请人：Orr Brian

  公开号：US20110071297A1

  公开（公告）日：2011-03-24

  The present disclosure generally relates to methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydromorphone, hydrocodone, or a derivative thereof, by means of a non-catalytic hydrogenation reaction of thebaine, oripavine or a derivative thereof, respectively, using a hydrazide reagent, followed by hydrolysis of the hydrogenated intermediate at a low temperature and for a short period of time. Additionally, the present disclosure relates to a composition comprising the desired hydromorphone, hydrocodone, or a derivative thereof, in combination with a 6-beta compound that is structurally related thereto.

  本公开涉及一般用于生产阿片类衍生物的方法。更具体地，本公开涉及通过非催化氢化反应分别使用肼酰肼试剂对吗啡碱、奥利帕碱或其衍生物进行制备羟吗啡、羟考酮或其衍生物，随后在低温下和短时间内对氢化中间体进行水解。此外，本公开还涉及一种包含所需的羟吗啡、羟考酮或其衍生物与结构相关的6-β化合物的组合物。
• PHENYLETHANOIC ACID, PHENYLPROPANOIC ACID AND PHENYLPROPENOIC ACID CONJUGATES AND PRODRUGS OF HYDROCODONE, METHOD OF MAKING AND USE THEREOF
  申请人：Mickle Travis

  公开号：US20110002991A1

  公开（公告）日：2011-01-06

  The presently described technology provides phenylethanoic acid, phenylpropanoic acid, phenylpropenoic acid, a salt thereof, a derivative thereof or a combination thereof chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs or compositions of hydrocodone which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

  目前描述的技术提供苯乙酸、苯丙酸、苯丙烯酸、其盐、其衍生物或其化学结合到羟考酮（吗啡酮-6-酮，4,5-α-环氧-3-甲氧基-17-甲基）以形成新型羟考酮的前药或组合物，其具有降低滥用羟考酮的潜力。该技术还提供了治疗患者的方法、药物配套和合成本技术结合物的方法。

表征谱图