甲乙双酮 | 115-67-3

• 物质功能分类: 原料药 - 神经系统用药 - 抗癫痫及抗惊厥药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 甲乙双酮
• 英文名称: paramethadione
• 英文别名: 5-ethyl-3,5-dimethyl-oxazolidine-2,4-dione；5-Aethyl-3,5-dimethyl-oxazolidin-2,4-dion；3,5-Dimethyl-5-ethyl-2,4-oxazoldion；Paramethadion；5-ethyl-3,5-dimethyl-1,3-oxazolidine-2,4-dione
• CAS: 115-67-3
• 化学式: C₇H₁₁NO₃
• mdl: MFCD00865309
• 分子量: 157.169
• InChiKey: VQASKUSHBVDKGU-UHFFFAOYSA-N

物化性质

• 熔点：
  31-32 °C
• 沸点：
  281.82°C (rough estimate)
• 密度：
  d425 1.1180-1.1240
• 物理描述：
  Liquid
• 颜色/状态：
  CLEAR, COLORLESS LIQUID
• 气味：
  FRUITY, ESTERLIKE ODOR
• 溶解度：
  8.4 mg/mL
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
• 折光率：
  INDEX OF REFRACTION: 1.449 @ 25 °C/D
• 保留指数：
  1120

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.714
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

主要在肝脏（主要通过细胞色素P450同种型2C9），帕拉甲酮完全脱甲基生成5-乙基-5-甲基-2,4-噁唑烷二酮，这是活性代谢物。

Primarily hepatic (mainly via cytochrome P450 isozyme 2C9), paramethadione is completely demethylated to 5-ethyl-5-methyl-2,4-oxazolidinedione, the active metabolite.

来源:DrugBank

代谢

paramethadione完全N-去甲基化成5-乙基-5-甲基恶唑烷-2,4-二酮...

PARAMETHADIONE IS COMPLETELY N-DEMETHYLATED TO 5-ETHYL-5-METHYL-OXAZOLIDINE-2,4-DIONE...

来源:Hazardous Substances Data Bank (HSDB)

代谢

PARAMETHADIONE IS N-DEMETHYLATED BY HEPATIC MICROSOMAL ENZYMES TO ACTIVE METABOLITE THAT IS SLOWLY EXCRETED IN URINE... 甲孕酮通过肝脏微粒体酶N-去甲基化，转化为活性代谢物，该代谢物在尿液中缓慢排泄...

PARAMETHADIONE IS N-DEMETHYLATED BY HEPATIC MICROSOMAL ENZYMES TO ACTIVE METABOLITE THAT IS SLOWLY EXCRETED IN URINE...

来源:Hazardous Substances Data Bank (HSDB)

代谢

帕梅撒多尼被肝脏微粒体酶N-去甲基化为活性代谢物...代谢物在长期用药期间积累，可能是母药抗惊厥活性的主要原因...

PARAMETHADIONE IS N-DEMETHYLATED BY HEPATIC MICROSOMAL ENZYMES TO ACTIVE METABOLITE... METABOLITE ACCUMULATES DURING CHRONIC MEDICATION & IS PROBABLY RESPONSIBLE FOR MOST OF ANTICONVULSANT ACTIVITY OF PARENT DRUG...

来源:Hazardous Substances Data Bank (HSDB)

代谢

主要在肝脏（主要通过细胞色素P450同种型2C9），帕拉米哒酮完全脱甲基生成5-乙基-5-甲基-2,4-噁唑烷二酮，这是活性代谢物。 半衰期：12到24小时（然而，活性代谢物的半衰期尚不清楚）

Primarily hepatic (mainly via cytochrome P450 isozyme 2C9), paramethadione is completely demethylated to 5-ethyl-5-methyl-2,4-oxazolidinedione, the active metabolite. Half Life: 12 to 24 hours (however the half-life for the active metabolite is not known)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

狄奥内抗惊厥药如Paramethadione可以减少丘脑神经元（包括丘脑传递神经元）的T型钙电流。这抑制了皮层-丘脑传递，并提高了丘脑重复活动的阈值。这导致了对异常的丘脑-皮层节律性的抑制，该节律性被认为是在失神发作期间在脑电图（EEG）上看到的3-Hz尖波-慢波放电的基础。

Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

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

可能会导致一种可能发展成史蒂文斯-约翰逊综合征的危险性皮疹，这是一种极为罕见但可能致命的皮肤病。

May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

通过消化道的快速通道。

Rapid via the digestive tract.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

过量症状包括笨拙或不稳定、昏迷、严重眩晕、极度嗜睡、严重恶心和视力问题。可能会导致一种可能发展成史蒂文斯-约翰逊综合症的危险性皮疹，这是一种极为罕见但可能致命的皮肤病。

Symptoms of overdose include clumsiness or unsteadiness, coma, severe dizziness, severe drowsiness, severe nausea, and problems with vision. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

通过消化道的快速通道。

Rapid via the digestive tract.

来源:DrugBank

吸收、分配和排泄

paramethadione完全N-去甲基化成5-乙基-5-甲基恶唑烷-2,4-二酮，并通过肾脏缓慢排泄。

PARAMETHADIONE IS COMPLETELY N-DEMETHYLATED TO 5-ETHYL-5-METHYL-OXAZOLIDINE-2,4-DIONE AND SLOWLY EXCRETED BY KIDNEYS.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2934999090

制备方法与用途

Parametadione（异噻二酮）是一种抗癫痫药物[1]。

反应信息

• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 四氯化碳 、 水 、 氯 作用下， 生成 甲乙双酮
  参考文献：
  名称：

  Davies et al., Journal of the Chemical Society, 1950, p. 34

  摘要：

  DOI：

文献信息

• 1-(2-PHENOXYMETHYLHETEROARYL)PIPERIDINE AND PIPERAZINE COMPOUNDS
  申请人：Stangeland Eric L.

  公开号：US20110230495A1

  公开（公告）日：2011-09-22

  The invention relates to compounds of formula I: where X, HAr, a, and R 1 through R 6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  本发明涉及如下公式I的化合物： 其中X，HAr，a，以及R1至R6如说明书所述，或其药用可接受的盐。公式I的化合物是5-羟色胺和去甲肾上腺素再摄取抑制剂。本发明还涉及包含这些化合物的药物组合物；使用这些化合物的方法；以及制备这些化合物的方法和中间体。
• [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。
• PYRIDINE AND PIPERIDINE DERIVATIVES AND USE THEREOF
  申请人：Purdue Pharma L.P.

  公开号：US20150141434A1

  公开（公告）日：2015-05-21

  The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I: or pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein R 1 , R 4 , X, G, n, p, W 1 , W 2 , W 3 , W 4 , and the E ring are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II-XIII as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.

  本发明提供了一种用作钠通道阻断剂的化合物。在一方面，本发明提供了公式I的化合物： 或其药用可接受的盐、溶剂化物、水合物或对映异构体，其中R1、R4、X、G、n、p、W1、W2、W3、W4和E环在公开中定义。在某些实施例中，本发明提供了上述公式II-XIII的化合物。本发明还提供了使用上述任何讨论公式的化合物来治疗对钠通道阻断有反应的疾病。在一个实施例中，发明化合物用于治疗疼痛。
• 2,5-DIALKYL-4-H/HALO/ETHER-PHENOL COMPOUNDS
  申请人：Tansna Therapeutics Inc.

  公开号：US20150148430A1

  公开（公告）日：2015-05-28

  The present disclosure provides phenolic compounds useful in the treatment of neurological conditions such as convulsions and tremors, having the structure of Formula (I): wherein R 2 , R 4 , & R 5 , are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating neurological conditions.

  本公开提供用于治疗诸如惊厥和震颤等神经学状况的酚类化合物，其具有公式（I）的结构： 其中R2、R4和R5如详细描述中定义；包含至少一种该化合物的药物组合物；以及用于治疗神经学状况的方法。
• [EN] 2,3,5 TRISUBSTITUTED ARYL AND HETEROARYL AMINO DERIVATIVES, COMPOSITIONS, AND METHODS OF USE<br/>[FR] DÉRIVÉS AMINÉS D'HÉTÉROARYLE ET D'ARYLE 2,3,5 TRISUBSTITUÉS, COMPOSITIONS ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：NEUROTHERAPEUTICS PHARMA INC

  公开号：WO2013059648A1

  公开（公告）日：2013-04-25

  Compounds are disclosed that have a formula represented by the following:(I) wherein Cy, L1 R1, R2a, R2b, R3, R4, n, and L2 are as described herein. These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example addictive disorders, Alzheimer's Disease, anxiety disorders, ascites, autism, bipolar disorder, cancer, depression, endothelial corneal dystrophy, edema, epilepsy, glaucoma, Huntington's Disease, inflammatory pain, insomnia, ischemia, migraine, migraine with aura, migraine without aura, neuropathic pain, nociceptive neuralgia, nociceptive pain, ocular diseases, pain, itch, excessive itch, Pruritis, neuropathic pruritis, Parkinson's disease, personality disorders, postherpetic neuralgia, psychosis, schizophrenia, seizure disorders, tinnitus, and withdrawal syndromes.

  已披露具有以下表示的化合物的公式：(I)，其中Cy、L1、R1、R2a、R2b、R3、R4、n和L2如本文所述。这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如成瘾障碍、阿尔茨海默病、焦虑障碍、腹水、自闭症、躁郁症、癌症、抑郁症、内皮角膜营养不良、水肿、癫痫、青光眼、亨廷顿病、炎症性疼痛、失眠、缺血、偏头痛、伴有先兆的偏头痛、无先兆的偏头痛、神经病性疼痛、伤害性神经痛、伤害性疼痛、眼部疾病、疼痛、瘙痒、过度瘙痒、瘙痒、神经性瘙痒、帕金森病、人格障碍、带状疱疹后神经痛、精神病、精神分裂症、癫痫障碍、耳鸣和戒断综合症等。

表征谱图