甲乙哌啶酮 | 125-64-4

• 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: 甲乙哌啶酮
• 中文别名: 甲普龙；甲双乙酮；甲乙哌酮；甲哌啶酮；甲双乙酮甲乙哌酮甲哌啶酮甲普龙
• 英文名称: methyprylon
• 英文别名: noludar；3,3-diethyl-5-methyl-piperidine-2,4-dione；3,3-Diaethyl-5-methyl-piperidin-2,4-dion；3,3-diethyl-5-methylpiperidine-2,4-dione
• CAS: 125-64-4
• 化学式: C₁₀H₁₇NO₂
• 分子量: 183.25
• InChiKey: SIDLZWOQUZRBRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

肝脏的。美替尔几近完全代谢。

Hepatic. Methyprylon is almost completely metabolized.

来源:DrugBank

代谢

从人类受试者的尿液中...提取了美替尔...已经鉴定出一个新的代谢物为2,4,6-三氧-3,3-二乙基-5-甲基哌啶。2,4-二氧-3,3-二乙基-5-甲基四氢吡啶，2,4-二氧-3,3-二乙基-5-羟基甲基四氢吡啶和4,6-二氧-5,5-二乙基-四氢尼古丁酸...被确定为代谢物...

FROM URINE OF HUMAN SUBJECTS ... TAKEN METHYPRYLON ... NEW METABOLITE HAS BEEN ... IDENTIFIED AS 2,4,6-TRIOXO-3,3-DIETHYL-5-METHYLPIPERIDINE. 2,4-DIOXO-3,3-DIETHYL-5-METHYLTETRAHYDROPYRIDINE, 2,4-DIOXO-3,3-DIETHYL-5-HYDROXYMETHYLTETRAHYDROPYRIDINE, & 4,6-DIOXO-5,5-DIETHYL-TETRAHYDRONICOTINIC ACID ... ESTABLISHED AS METABOLITES ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

虽然已知甲基哌啶酮的代谢降解过程，但还不确定这一过程发生在哪个器官。甲基哌啶酮被脱氢成5-甲基-吡啶二酮，然后部分氧化成羟基衍生物，最终氧化成5-羧基-吡啶二酮。羟基衍生物大约有38%与人类血浆蛋白结合。还可能产生其他不太重要的代谢物，但代谢物部分与葡萄糖醛酸结合，大约有97%的母药被代谢。完整的甲基哌啶酮（3%）和其代谢物（60%）在尿液中回收，而大约20%在粪便中找到，这表明药物发生了肠肝循环。

While the metabolic degradation of methyprylon is known, it is not certain in which organ this takes place. Methyprylon is dehydrogenated to 5-methyl-pyrithyldione, then partially oxidized to hydroxy derivatives, and finally oxidized to 5-carboxy-pyrithyldione. The hydroxy derivatives are bound approximately 38% to human plasma proteins. Other less important metabolites may arise, but the metabolites are partly conjugated to glucuronide, with approximately 97% of the parent drug being metabolized. Intact methyprylon (3%) and its metabolites (60%) are recovered in the urine, while approximately 20% is found in the feces, demonstrating that enterohepatic circulation of the drug occurs.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏的。美替尔完全被代谢。 半衰期：6-16小时

Hepatic. Methyprylon is almost completely metabolized. Half Life: 6-16 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Methyprylon 结合在一个与 GABA_A 受体上的 Cl^- 离子通道相关联的独特结合位点，增加了 Cl^- 离子通道开放的时间长度。因此，GABA 在丘脑中的突触后抑制效应被延长。

Methyprylon binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

它们会导致说话含糊不清、迷失方向和“醉酒”行为。它们在身体和心理上都具有成瘾性。

They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

过量症状包括兴奋和抽搐。

Symptoms of overdose include excitation and convulsions.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

酒精增强了甲基戊巴比妥的效果。

Alcohol potentiates the effect of methyprylon.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

药物在肠道中被良好吸收。

DRUG IS WELL ABSORBED FROM INTESTINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

它的水溶性比 GLUTETHIMIDE 更强，但尚不清楚胃肠道吸收是否因此变得不那么不稳定。只有3%以原形从尿液中排出。只有60%的自由代谢物和葡萄糖苷酸可以从尿液中回收。

IT IS MORE WATER SOL THAN GLUTETHIMIDE, BUT IT IS NOT KNOWN WHETHER GI ABSORPTION IS CONSEQUENTLY LESS ERRATIC. ... ONLY 3% IS EXCRETED IN URINE UNCHANGED. ... ONLY 60% OF FREE METABOLITES & GLUCURONIDES IS RECOVERABLE FROM URINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

治疗性血药浓度可能不超过1.0毫克/100毫升。成人单次口服650毫克后，大约在2小时后达到最高血浆浓度约1.0毫克/100毫升。在致命案例中，据报道血药浓度超过9.0毫克/100毫升。

THERAPEUTIC BLOOD CONCN PROBABLY DO NOT EXCEED 1.0 MG/100 ML. FOLLOWING SINGLE ORAL DOSE OF 650 MG IN ADULTS, MAX PLASMA CONCN OF APPROX 1.0 MG/100 ML IS REACHED AFTER 2 HR. IN FATAL CASES, BLOOD CONCN IN EXCESS OF 9.0 MG/100 ML HAVE BEEN REPORTED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Methyprylon does not accumulate selectively in organ systems. 甲基戊二醛不会在器官系统中选择性累积。

Methyprylon does not accumulate selectively in organ systems.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  甲乙哌啶酮 生成 ethyl 3-(2-ethylbutanoylamino)-2-methylpropanoate
  参考文献：
  名称：

  SUGDEN, J. K.;WOOD, E. J. A., PHARMAC. ACTA HELV., 1981, 56, N 9-10, 302-303

  摘要：

  DOI：
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 丙酮 作用下， 生成 甲乙哌啶酮
  参考文献：
  名称：

  SOPTANTE SPALTUNG von2,4-Dioxo-3,3-diäthyl-5-methyl-piperidinin Optischen Antipoden

  摘要：

  通过在各种溶剂（例如甲醇，丙酮，丁醇，水等）中约400次结晶，将2，4-二氧代3，3-二乙基-5-甲基-哌啶自发地拆分为其旋光对映体。在分辨过程中的行为，必须得出结论，其光学对映体形成混合晶体。报道了光学活性材料在各种溶剂中的外消旋混合速率。（+）-2，4-Dioxo-3，3-diethyl-5-methyl-perperidine作为催眠药比其（-）-正电极更具活性。

  DOI：

  10.1002/hlca.19560390526

文献信息

• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE LA QUINOLIZIDINONE
  申请人：MERCK & CO INC

  公开号：WO2009051715A1

  公开（公告）日：2009-04-23

  The present invention is directed to spiropiperidine compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的螺环哌啶化合物，这些化合物是M1受体阳性变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍方面有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• MULTIFUNCTIONAL SMALL MOLECULES
  申请人：Baker, JR. James R.

  公开号：US20120259114A1

  公开（公告）日：2012-10-11

  The present invention relates to dendrimer synthesis. Specifically, the present invention relates to triazine scaffolds capable of click chemistry for one-step synthesis of functionalized dendrimers, and methods of making and using the same.

  本发明涉及树枝状大分子的合成。具体而言，本发明涉及能够进行点击化学的 三嗪支架，用于一步法合成功能化树枝状大分子，以及制造和使用该支架的方法。
• [EN] 3-(1H-PYRAZOL-4-YL)PYRIDINE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR<br/>[FR] MODULATEURS ALLOSTÉRIQUES DE TYPE 3-(1H-PYRAZOL-4-YL)PYRIDINE DU RÉCEPTEUR MUSCARINIQUE M4 DE L'ACÉTYLCHOLINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2019005588A1

  公开（公告）日：2019-01-03

  The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

  本发明涉及吡唑并[4,3-b]吡啶化合物，其为M4毒蕈碱型乙酰胆碱受体的变构调节剂。本发明还涉及在可能治疗或预防神经和精神障碍以及涉及M4毒蕈碱型乙酰胆碱受体的疾病中使用所述化合物。本发明还涉及包含这些化合物的组合物。本发明还涉及在可能预防或治疗涉及M4毒蕈碱型乙酰胆碱受体的疾病中使用这些组合物。

表征谱图