DL-alpha-普鲁丁 | 77-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: DL-alpha-普鲁丁
• 英文名称: (+/-)-α-prodine
• 英文别名: alphaprodine；(+/-)-1,3r-dimethyl-4t-phenyl-4c-propionyloxy-piperidine；(+/-)-1,3r-Dimethyl-4t-phenyl-4c-propionyloxy-piperidin；(+/-)-Alphaprodin；(+/-)-Alpkaprodin；dl-alpha-Prodine；[(3R,4S)-1,3-dimethyl-4-phenylpiperidin-4-yl] propanoate
• CAS: 77-20-3；468-59-7；15867-21-7；23950-19-8；25123-05-1；25123-06-2；25312-58-7；25312-59-8；51264-03-0
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: UVAZQQHAVMNMHE-CJNGLKHVSA-N

物化性质

• 沸点：
  120-135 °C(Press: 1.5 Torr)
• 密度：
  1.06±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷
• 颜色/状态：
  WHITE, CRYSTALLINE POWDER
• 分解：
  When heated to decomp it emits very toxic fumes of oxides of nitrogen and hydrogen chloride. /alpha-prodine hydrochloride/

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

在给狗静脉注射后，从尿液中唯一可提取的代谢物是去甲阿尔法普罗定。

FOLLOWING IV ADMIN TO DOGS THE ONLY EXTRACTABLE METABOLITE FROM URINE WAS NORALPHAPRODINE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

盐酸阿普罗定的镇静作用会被巴比妥类药物、全身麻醉剂和某些吩噻嗪类药物增强。因此，在与这些药物同时使用时应减少剂量。/盐酸阿普罗定/

DEPRESSANT EFFECTS OF ALPHAPRODINE HYDROCHLORIDE ARE POTENTIATED BY BARBITURATES, GENERAL ANESTHETIC AGENTS, & SOME PHENOTHIAZINES. THUS, THE DOSE SHOULD BE REDUCED WHEN USED CONCOMITANTLY WITH SUCH AGENTS. /ALPHAPRODINE HYDROCHLORIDE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

使用哌替啶和苯乙肼或其他单胺氧化酶抑制剂可能对中枢神经系统产生兴奋和抑制作用，导致深度昏迷和死亡。/哌替啶/

CONCURRENT ADMIN OF MEPERIDINE & PHENELZINE OR OTHER MONOAMINE OXIDASE INHIBITORS MAY RESULT IN EXCITATORY & DEPRESSANT EFFECTS ON THE CNS LEADING TO DEEP COMA & DEATH. /MEPERIDINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

可能会形成习惯。

May be habit forming.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

不良影响包括偶尔的呼吸抑制、眩晕、嗜睡、出汗和荨麻疹；很少见的情况下，可能会出现恶心、呕吐、不安和混乱。/盐酸阿法罗定/

ADVERSE EFFECTS INCLUDE OCCASIONAL RESP DEPRESSION, DIZZINESS, DROWSINESS, SWEATING & URTICARIA; RARELY, NAUSEA, VOMITING, RESTLESSNESS, & CONFUSION MAY OCCUR. /ALPHAPRODINE HYDROCHLORIDE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

过敏现象在使用阿片类止痛药时会发生，但并不常见。它们通常表现为荨麻疹和其他类型的皮疹，如固定性药疹和接触性皮炎，在护士和制药工作者中也会发生。吗啡及其相关药物注射部位的肿块可能是由于释放的组织胺引起的。/阿片类药物/

ALLERGIC PHENOMENA OCCUR WITH OPIOID ANALGESICS, BUT ... NOT COMMON. THEY ARE USUALLY MANIFESTED AS URTICARIA & OTHER TYPES OF SKIN RASHES SUCH AS FIXED ERUPTIONS CONTACT DERMATITIS IN NURSES & PHARMACEUTICAL WORKERS ALSO OCCURS. WHEALS @ SITE OF INJECTION OF MORPHINE ... & RELATED DRUGS ARE PROBABLY CAUSED BY THE RELEASED HISTAMINE. /OPIOIDS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给狗静脉注射后，阿法罗定从血浆中迅速消失，并且具有较大的分布体积，这与它的快速起效和短时作用相符合。大脑和血浆之间似乎存在快速平衡。

FOLLOWING IV ADMIN TO DOGS, RAPID DISAPPEARANCE OF ALPHAPRODINE FROM PLASMA & LARGE DISTRIBUTION VOL WERE IN KEEPING WITH ITS RAPID ONSET & SHORT DURATION OF ACTION. THERE APPEARED TO BE RAPID EQUILIBRIUM BETWEEN BRAIN & PLASMA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿普洛丁的消除半衰期是131分钟（大约2小时），与美喷丁的247分钟相比。阿普洛丁和美喷丁的血浆清除率几乎相同：分别为1.04和1.01升/千克/分钟。尽管美喷丁在肝脏中广泛生物转化为N-去甲基衍生物和美喷丁酸（参见美喷丁），但目前没有关于阿普洛丁在人体内生物转化的信息。

The elimination half-life of alphaprodine is 131 minutes (approximately 2 hours) compared with 247 minutes for meperidine. Plasma clearances for alphaprodine and meperidine are nearly identical: 1.04 and 1.01 l/kg/min, respectively. Although meperidine undergoes extensive biotransformation in the liver to form N-demethylated derivatives and meperidinic acid (see Meperidine) no information is available relating to alphaprodine biotransformation in man.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿尔法普罗定从注射部位迅速吸收。35毫克阿尔法普罗定静脉给药产生的血药浓度与100毫克美沙酮后的血药浓度相似。阿尔法普罗定的半衰期（吸收）为4.6分钟，而美沙酮的半衰期为17.2分钟。

Alphaprodine is immediately absorbed from parenteral sites. Thirty-five milligrams of alphaprodine intravenously produces plasma concentrations similar to those following 100 mg meperidine. The half-life (absorption) is 4.6 minutes for alphaprodine compared with 17.2 minutes for meperidine.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  DL-alpha-普鲁丁 在 盐酸 、 氢氧化钾 、 potassium carbonate 、 溶剂黄146 、 锌 作用下， 以 乙醇 、 异丙醇 、 甲苯 为溶剂， 反应 124.0h， 生成 (3R,4S)-1-(1-cyanocyclohexyl)-4-hydroxy-3-methyl-4-phenylpiperidine
  参考文献：
  名称：

  苯环利定的一些异构衍生物的阿片样物质性质。

  摘要：

  苯环类类似物（+/-）-α-，（+/-）-β-和（+）-α-和（-）-α-4-羟基-3-甲基-4-苯基-1-已经制备了（1-苯基环己基）哌啶，均具有已知的相对和绝对立体化学，并且它们的镇痛作用与相应的脯氨酸有关。与脯氨酸相比，（+/-）-α-苯环利定类似物比其非对映异构体具有更强的镇痛作用，而与脯氨酸系列中的观察结果一致，3R，4S-α-对映异构体的药效远高于其非对映异构体。镜像形式。

  DOI：

  10.1111/j.2042-7158.1992.tb14356.x
• 作为产物：
  描述：

  (+/-)-α-4-hydroxy-3-methyl-4-phenylpiperidine 在 吡啶 、 甲酸 作用下， 反应 8.0h， 生成 DL-alpha-普鲁丁
  参考文献：
  名称：

  Common stereospecificity of opioid and dopamine systems for N-butyrophenone prodine-like compounds

  摘要：

  The two optical isomers of 1-[3-(p-fluorobenzoyl)propyl]-3-methyl-4-phenyl-4-propionoxypiperidine (FPP) were obtained by resolution of (+/-)-r-3-methyl-4-phenyl-c-4-piperidinol followed by N-alkylation and O-propionylation. These, as well as the racemate, were evaluated for their antinociceptive, opioid, and neuroleptic properties using in vivo and in vitro test systems. The results are remarkable in two respect, namely, the dextrorotatory isomer is consistently the most potent on all tests, and it acts on both opioid (mu) and neuroleptic (D2) receptors.

  DOI：

  10.1021/jm00105a029

文献信息

• PYRAZOLYL PYRIMIDINONE COMPOUNDS AND THE USES THEREOF
  申请人：Purdue Research Foundation

  公开号：US20210100797A1

  公开（公告）日：2021-04-08

  The present invention relates to a method of treatment for chronic pain, opioid dependence, alcohol use disorder or autism using a class of pyrimidinone compounds, an adenylyl cyclase 1 (AC1) inhibitor. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases in mammals using those compounds disclosed herein.

  本发明涉及一种使用嘧啶酮化合物类治疗慢性疼痛、阿片类药物依赖、酒精使用障碍或自闭症的方法，该化合物为腺苷酸环化酶1（AC1）抑制剂。本发明还涉及使用本文所述化合物的药物组合物和用于治疗哺乳动物疾病的方法。
• METHODS AND COMPOSITIONS FOR PREVENTING OPIOID ABUSE
  申请人：Waterville Valley Technologies, Inc.

  公开号：US20160326182A1

  公开（公告）日：2016-11-10

  Abuse-resistant opioid compounds, drug delivery systems, pharmaceutical compositions comprising an opioid covalently bound to a chemical moiety are provided. Methods of delivering an active ingredient to a subject and methods of preventing opioid abuse are also provided.

  提供了耐滥用的阿片类化合物、药物输送系统、含有阿片类药物与化学基团共价结合的制药组合物。还提供了将活性成分输送给受试者的方法以及预防阿片类药物滥用的方法。
• [EN] ADENOSINE ANALOGS FOR THE TREATMENT OF DISEASE<br/>[FR] ANALOGUES D'ADÉNOSINE POUR LE TRAITEMENT D'UNE MALADIE
  申请人：BIOINTERVENE INC

  公开号：WO2020247546A1

  公开（公告）日：2020-12-10

  The disclosure provides adenosine analogs for the treatment of disease such as pain and inflammatory conditions.

  该披露提供了用于治疗疾病，如疼痛和炎症症状的腺苷类似物。
• [EN] SYNTHESIS OF METABOLICALLY STABLE ANALGESICS, PAIN MEDICATIONS AND OTHER AGENTS<br/>[FR] SYNTHÈSE D'ANALGÉSIQUES À MÉTABOLISME STABLE, DE MÉDICAMENTS CONTRE LA DOULEUR ET D'AUTRES AGENTS
  申请人：HUMAN BIOMOLECULAR RES INST

  公开号：WO2005117589A1

  公开（公告）日：2005-12-15

  Disclosed are analgesic-related compositions and methods of using the compositions for modulation of analgesic receptor activity. The compositions and methods are useful for reducing pain, as well as for therapeutic intervention of addictions or other diseases or disorders amenable to treatment or prophylaxis by modulation of analgesic receptor signaling.

  揭示了与止痛相关的组合物及使用这些组合物调节止痛受体活性的方法。这些组合物和方法对于减轻疼痛以及治疗成瘾或其他可通过调节止痛受体信号传导进行治疗或预防的疾病或障碍是有用的。
• [EN] A3 ADENOSINE RECEPTOR AGONISTS FOR USE IN MEDICINE<br/>[FR] ANALOGUES DU RÉCEPTEUR A3 DE L'ADÉNOSINE POUR LE TRAITEMENT D'UNE MALADIE
  申请人：BIOINTERVENE INC

  公开号：WO2022040241A1

  公开（公告）日：2022-02-24

  The disclosure provides adenosine analogs for the treatment of disease such as pain and inflammatory conditions.

  该披露提供了用于治疗疾病如疼痛和炎症症状的腺苷类似物。

表征谱图