乙烯啡 | 14521-96-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 中文名称: 乙烯啡
• 中文别名: 依托啡；埃托啡
• 英文名称: etorphine
• 英文别名: (1R,2S,6R,14R,15R,19R)-19-[(2R)-2-hydroxypentan-2-yl]-15-methoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,16-tetraen-11-ol
• CAS: 14521-96-1
• 化学式: C₂₅H₃₃NO₄
• 分子量: 411.541
• InChiKey: CAHCBJPUTCKATP-FAWZKKEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

毒理性

• 解毒与急救

紧急和支持性措施：保持呼吸道通畅，必要时协助呼吸。给予补充氧气。如果出现昏迷、癫痫、低血压和非心源性肺水肿，则进行治疗。/阿片类药物和鸦片类物质/

Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, hypotension, and noncardiogenic pulmonary edema if they occur. /Opiates and opioids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

特异性的药物和解毒剂：纳洛酮是一种特异性的阿片类药物拮抗剂，本身没有激动剂特性；可以安全地给予大剂量。 ... 注意：纳洛酮的持续时间（1-2小时）短于许多阿片类药物。因此，在最后一次给予纳洛酮至少3-4小时之后，才能释放已经苏醒的病人。通常，如果需要纳洛酮来逆转阿片类药物引起的昏迷，为了安全起见，最好将病人收入院至少观察6-12小时。纳美芬是一种作用时间更长的阿片类药物拮抗剂（3-5小时）。 ... /阿片类药物和鸦片类物质/

Specific drugs and antidotes: Naloxone is a specific opioid antagonist with no agonist properties of its own; large doses may be given safely. ... Caution: The duration of effect of naloxone (1-2 hours) is shorter than that of many opioids. Therefore, do not release a patient who has awakened after naloxone treatment until at least 3-4 hours has passed since the last dose of naloxone. In general, if naloxone was required to reverse opioid-induced coma, it is safer to admit the patient for at least 6-12 hours of observation. Nalmefene is an opioid antagonist with a longer duration of effect (3-5 hours). ... /Opiates and opioids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

去污。如果条件适当，口服活性炭。在小到中等摄入量后，如果能及时给予活性炭，则无需进行洗胃。... /阿片类药物和镇痛剂/

Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. ... /Opiates and opioids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

增强消除。由于阿片类药物的分布量非常大，且存在有效的解毒治疗方法，因此增强消除程序并无作用。/阿片类药物和鸦片类药物/

Enhanced elimination. Because of the very large volumes of distribution of the opioids and the availability of an effective antidotal treatment, there is no role for enhanced elimination procedures. /Opiates and opioids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人体暴露研究/ 酮基芬，一种强效的吗啡样药物，其效果与吗啡进行了定性和定量比较。在非依赖性受试者中，酮基芬的剂量为0.025、0.050和0.100毫克时，能产生瞳孔收缩和类似吗啡的主观效果以及欣快感。酮基芬的效力是吗啡的500倍，具有非常快速的作用发作和短暂的作用持续时间。在吗啡依赖性受试者中，酮基芬抑制了戒断症状，但持续时间比吗啡短。这些研究表明，在人体中，酮基芬是一种具有高滥用潜力的类似吗啡的药物。

/HUMAN EXPOSURE STUDIES/ The effects of etorphine, a potent morphine-like drug, were qualitatively and quantitatively compared to those of morphine. In nondependent subjects, etorphine in doses of 0.025, 0.050, and 0.100 mg produced pupillary constriction and morphine-like subjective effects and euphoria. Etorphine was 500 times as potent as morphine, with a very rapid onset and short duration of action. In morphine-dependent subjects, etorphine suppressed abstinence but for a shorter period than morphine. These studies indicate that in man etorphine is a morphine-like drug with a high abuse potential.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

11头幼年非洲象被给予盐酸埃托啡（2.19 ± 0.11微克/千克体重；平均值 ± 标准差）作为单次肌内注射；3头大象额外给予了埃托啡（0.42 ± 0.09微克/千克）静脉注射。在麻醉后，每头大象通过给予0.5%的氟烷/氧气混合物或者多次静脉注射埃托啡来维持侧卧位。在注射后0.25小时和0.5小时以及此后每30分钟，通过耳动脉收集血液样本，并使用放射免疫分析法测定埃托啡的血清浓度。在单次肌内注射并随后用氟烷和氧气维持的6头大象中，埃托啡的最高平均血清浓度在注射后0.5小时为1.62 ± 0.97纳克/毫升；此后，平均血清浓度稳步下降。在用多次静脉注射埃托啡维持侧卧位的4头大象中，没有发现觉醒初期征兆出现时间与觉醒前埃托啡血清浓度之间的相关性。在给予初步麻醉剂量的埃托啡后，静脉注射埃托啡的间隔时间缩短。/盐酸埃托啡/

Eleven juvenile African elephants were given etorphine hydrochloride (2.19 +/- 0.11 micrograms/kg of body weight; mean +/- SD) as a single IM injection; 3 elephants were given additional etorphine (0.42 +/- 0.09 micrograms/kg) IV. After immobilization, each elephant was maintained in lateral recumbency by administration of a 0.5% halothane/oxygen mixture or by administration of multiple IV injections of etorphine. At postinjection hours 0.25 and 0.5 and at 30-minute intervals thereafter, blood samples were collected via an auricular artery, and serum concentrations of etorphine were determined by use of radioimmunoassay. The highest mean serum concentration of etorphine in 6 elephants given a single IM injection and subsequently maintained on halothane and oxygen was 1.62 +/- 0.97 ng/mL at postinjection hours 0.5; thereafter, the mean serum concentration decreased steadily. In 4 elephants maintained in lateral recumbency with multiple IV administrations of etorphine, a correlation was not found between the time to develop initial signs of arousal and serum concentrations of etorphine before arousal. After administration of the initial immobilizing dose of etorphine, the interval between successive IV administrations of etorphine decreased. /Etorphine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一个涉及Immobilon商业配方的法医案件中，死后采集的股静脉和心脏血液样本中测得的埃托啡浓度分别为14.5和23.5微克/升。尿液中未检测到埃托啡。

In a forensic case involving Immobilon /commerical formulation/, the etorphine concentrations measured in postmortem femoral vein and heart blood specimens were 14.5 and 23.5 ug/L, respectively. No etorphine was detected in the urine.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  乙烯啡 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 22.0~65.0 ℃ 、1.5 MPa 条件下， 反应 24.0h， 以77%的产率得到二氢埃托啡
  参考文献：
  名称：

  [EN] IMPROVED METHOD OF MANUFACTURING BUPRENORPHINE AND ANALOGUES THEREOF FROM ORIPAVINE
  [FR] PROCÉDÉ AMÉLIORÉ DE FABRICATION DE BUPRÉNORPHINE ET D'ANALOGUES DE CELLE-CI À PARTIR D'ORIPAVINE

  摘要：

  该发明涉及一种改进的制备丁丙诺啡、其盐、丁丙诺啡类似物及其盐的方法。具体而言，该发明涉及一种以经济和生态方式制备丁丙诺啡及相关产品和盐的方法，其产量增加。

  公开号：

  WO2016078833A1
• 作为产物：
  描述：

  可待因 在 lithium aluminium tetrahydride 、 草酰氯 、 potassium tert-butylate 、 potassium carbonate 、 magnesium 、 二甲基亚砜 、 苯硫酚 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醚 、 二氯甲烷 、 氯仿 为溶剂， 反应 13.75h， 生成 乙烯啡
  参考文献：
  名称：

  从可待因中轻松合成和合成乙内啡肽和二氢埃托啡结构

  摘要：

  在这项研究中，描述了一种改进的由可待因合成甲乙啡和二氢埃托啡的方法，总收率分别为2.7％和1.5％。X射线结构分析验证了19-丙基乙烯醇7的结构。该结果有望用于合成各种基于吗啡的药物。

  DOI：

  10.1002/jccs.201190048

文献信息

• Sustained-release analgesic compounds
  申请人：——

  公开号：US20030022876A1

  公开（公告）日：2003-01-30

  A pharmaceutically active inventive compound comprises two independently active analgesic moieties covalently conjoined through a physiologically labile linker. A preferred embodiment comprises an opioid, such as morphine, covalently linked to at least one analgesic compound selected from the group consisting of an opioid or a non-opioid compound through a physiologically labile linker. Suitable covalent linkers are covalently bonded to the two independently active analgesic compounds through one or more lactone, lactam, or sulfonamido linkages. Suitable linkers include endogenous carboxylate, amido, and sulfonamido moieties, and exogenous moieties that form the aforementioned lactone, lactam or sulfonamido linkages.

  一种药理活性的创新化合物包括通过生理易降解的连接物共价连接的两个独立活性镇痛基团。一种首选实施例包括阿片类药物，如吗啡，通过生理易降解的连接物与来自阿片类或非阿片类化合物组成的群中选择的至少一种镇痛化合物共价连接。适当的共价连接物通过一个或多个内源的内酯、内酰胺或磺酰胺连接而与这两个独立活性的镇痛化合物共价结合。适当的连接物包括内源的羧酸酯、酰胺和磺酰胺基团，以及形成上述内酯、内酰胺或磺酰胺连接的外源基团。
• Controlled-release compositions containing opioid agonist and antagonist
  申请人：——

  公开号：US20020010127A1

  公开（公告）日：2002-01-24

  Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

  含有阿片激动剂、阿片拮抗剂和受控释放材料的控释剂型，其在给药间隔期间释放阿片激动剂的镇痛或亚镇痛量以及足以减轻所述阿片激动剂的副作用的阿片拮抗剂的量。当给予人类患者时，该剂型提供至少约8小时的镇痛作用。在其他实施例中，给药间隔期释放的拮抗剂剂量增强了阿片激动剂的镇痛效力。
• [EN] COMBINATION THERAPY FOR PREVENTING ADDICTION<br/>[FR] POLYTHÉRAPIE POUR LA PRÉVENTION D'UNE ADDICTION
  申请人：AMYGDALA NEUROSCIENCES INC

  公开号：WO2019079209A1

  公开（公告）日：2019-04-25

  Disclosed is a novel combination therapy to reduce or prevent the acquisition of a conditioned response in a mammal comprising administering to the mammal a therapeutically effective amount of an aldehyde dehydrogenase (ALDH-2) inhibitor compound, such as a compound of Formula (I), in combination with a substance that produces the conditioned response, such as a medication containing a dopamine-producing agent such as an opioid, whereby the combination acts to reduce or prevent the acquisition of a conditioned response, and the deleterious side-effect of misuse, dependence, abuse, and/or addiction.

  揭示了一种新颖的联合疗法，用于减少或预防哺乳动物获得条件反射，包括向哺乳动物施用治疗有效量的醛脱氢酶（ALDH-2）抑制剂化合物，例如公式（I）中的化合物，与产生条件反射的物质结合，例如含有多巴胺生成剂的药物，如阿片类药物，从而使该组合作用于减少或预防条件反射的获得，以及滥用、依赖、滥用和/或成瘾的有害副作用。
• PYRIMIDINE COMPOUNDS AS DELTA OPIOID RECEPTOR MODULATORS
  申请人：COATS STEVEN J.

  公开号：US20110105520A1

  公开（公告）日：2011-05-05

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R 1 , R 2 , R 3 , and L, A, and R a are defined herein.

  公开了用于治疗各种疾病、综合征、状况和失调，包括疼痛的化合物、组合物和方法。这些化合物由以下式I表示： 其中R1、R2、R3和L、A、Ra在本文中定义。
• [EN] BUPRENORPHINE ANALOGS<br/>[FR] ANALOGUES DE BUPRÉNORPHINE
  申请人：PURDUE PHARMA LP

  公开号：WO2012038813A1

  公开（公告）日：2012-03-29

  The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R1, R2, R8, R 3a, R 3b, G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及如下所示的公式(I)、公式(IA)或公式(IB)的丁丙诺啡类似物化合物，其中R1、R2、R8、R 3a、R 3b、G、X、Z和Y的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及通过阿片类和ORL-1受体的活性调节的其他状况。