乙酮恶嗪 | 702-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 乙酮恶嗪
• 中文别名: 二乙恶酮；地沙双酮
• 英文名称: Diethadione
• 英文别名: 5,5-diethyl-[1,3]oxazinane-2,4-dione；5,5-diethyl-dihydro-[1,3]oxazine-2,4-dione；5,5-Diaethyl-dihydro-[1,3]oxazin-2,4-dion；5,5-diethyldihydro-2H-1,3-oxazine-2,4(3H)-dione；5,5-diethyl-1,3-oxazinane-2,4-dione
• CAS: 702-54-5
• 化学式: C₈H₁₃NO₃
• mdl: MFCD00864194
• 分子量: 171.196
• InChiKey: ORTYMGHCFWKXHO-UHFFFAOYSA-N

物化性质

• 熔点：
  97-98°
• 沸点：
  301.17°C (rough estimate)
• 密度：
  1.1998 (rough estimate)
• 颜色/状态：
  CRYSTALS FROM ETHER
• 保留指数：
  1395;1405

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 相互作用

抗癫痫药物在给药1-4天前对二恶烷的惊厥效果的影响在小鼠中进行了研究。当甲基苯巴比妥、普里米酮和美妥因在二恶烷给药前2天给药时，增强了这种效果。苯妥英钠在前2天具有抗惊厥作用，在4天后，引起50%动物惊厥所需的二恶烷剂量减少了。

EFFECTS OF ANTIEPILEPTIC DRUGS ADMINISTERED 1-4 DAYS BEFORE ON CONVULSANT EFFECTS OF DIOXONE WERE STUDIED IN MICE. METHYLPHENOBARBITAL, PRIMIDONE & METHOIN ENHANCED THE EFFECT WHEN GIVEN 2 DAYS PRIOR TO DIOXONE ADMINISTRATION. SODIUM PHENYTOIN HAD AN ANTICONVULSANT EFFECT IN THE FIRST 2 DAYS & AFTER 4 DAYS THE DOSAGE OF DIOXONE NECESSARY TO INDUCE CONVULSIONS IN 50 OF THE ANIMALS WAS DIMINISHED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

迷幻剂、戊巴比妥钠和羟基酮通过使用二乙二硫醚进行催眠滴定，在50只小鼠中以催眠为滴定终点。二乙二硫醚对催眠的拮抗作用可能是竞争性的，也可能是非竞争性的。

THE HYPNOTICS, PENTOBARBITONE SODIUM & HYDROXYDIONE WERE TITRATED BY DIETHADIONE USING HYPNOSIS IN 50 MICE AS THE TITRATION END-POINT. ANTAGONISM OF HYPNOSIS BY DIETHADIONE MAY BE COMPETITIVE OR NONCOMPETITIVE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

要维持50只小鼠在逐渐增加的催醒剂（如贝美格、二乙醑、毒扁豆碱、戊四唑和β-螺环戊烷戊二酰胺）存在下的催眠滴定终点，所需的催眠剂量、戊巴比妥钠的数量进行了研究。除了毒扁豆碱外，滴定曲线在高剂量时显示出斜率的反转，而二乙醑增强了催眠药的抑制效应。这些催醒剂和催眠药可能都在同一兴奋性突触上发挥作用，前者作为激动剂，后者作为竞争性或非竞争性拮抗剂。

THE QUANTITY OF HYPNOTIC, AMYLOBARBITONE SODIUM, REQUIRED TO MAINTAIN THE TITRATION END-POINT HYPNOSIS IN 50 MICE IN PRESENCE OF INCREASING DOSES OF ANALEPTICS SUCH AS BEMEGRIDE, DIETHADIONE, PICROTOXIN, PENTYLENETETRAZOLE, & BETA-SPIROCYCLOPENTANEGLUTARIMIDE WAS STUDIED. WITH THE EXCEPTION OF PICROTOXIN, TITRATION CURVES SHOWED A REVERSAL IN SLOPE AT THE HIGHEST DOSES, & DIETHADIONE ENHANCED THE DEPRESSANT ACTION OF THE HYPNOTIC. THESE ANALEPTICS & THE HYPNOTIC PROBABLY ALL ACT AT THE SAME EXCITATORY SYNAPSES, THE FORMER AS AGONISTS & THE LATTER AS COMPETITIVE OR NONCOMPETITIVE ANTAGONIST.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

DIOXONE在以0.05-20毫克/千克剂量静脉注射到兔子体内，30秒内对心脏活动没有影响。然而，当快速注射时，有时会引起短暂的心动过缓和心律不齐。

DIOXONE HAS NO EFFECT ON THE CARDIAC ACTIVITY WHEN INJECTED IV AT 0.05-20 MG/KG INTO RABBITS DURING 30 SECONDS. HOWEVER, WHEN RAPIDLY INJECTED, IT SOMETIMES CAUSED A TRANSIENT BRADYCARDIA & ARRHYTHMIA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠和兔血清中，二噁烷主要与球蛋白结合，同时也有一部分与白蛋白结合。

IN RAT & RABBIT SERUM DIOXONE WAS BOUND MAINLY BY GLOBULINS & A SMALL EXTENT ALSO BY ALBUMINS.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  乙酮恶嗪 在 tetraphosphorus decasulfide 作用下， 生成 5,5-diethyl-dihydro-[1,3]oxazine-2,4-dithione
  参考文献：
  名称：

  5,5-Disubstituted Dihydro-1,3-oxazine-2,4-diones. Research on Compounds Active on Central Nervous System. XII^1a

  摘要：

  DOI：

  10.1021/jo01094a026
• 作为试剂：
  描述：

  N1-(4-chloro-6-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl)cyclohexane-1,3-diamine 、 环丁酮 、 氰基硼氢化钠 在 氯化锌 乙酮恶嗪 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 17.37h， 以10 mM ammonium acetate in water over 12 minutes at a flow rate of 50 mL/minutes to provide the title compound (26 mg, 0.066 mmol, 16% yield)的产率得到乙酸铵
  参考文献：
  名称：

  PYRROLOPYRIDINE INHIBITORS OF KINASES

  摘要：

  本发明涉及公式（I）的化合物或药物可接受的盐，其中R1a，R1b，R1c，X和Y在说明书中有定义。本发明还涉及含有所述化合物的组合物，其对抑制Cdc7等激酶有用，并且用于治疗癌症等疾病的方法。

  公开号：

  US20110015173A1

文献信息

• [EN] SPIRO-SUBSTITUTED OXINDOLE DERIVATIVES HAVING AMPK ACTIVITY<br/>[FR] DÉRIVÉS D'OXINDOLE SPIRO-SUBSTITUÉS AYANT UNE ACTIVITÉ SUR AMPK
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014202580A1

  公开（公告）日：2014-12-24

  The present invention relates to compounds of formula (I), which have valuable pharmacological properties, in particular are activators of AMPK and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this receptor. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.

  本发明涉及具有有价值的药理特性的式(I)化合物，特别是AMPK激活剂，因此在治疗某些可以通过激活该受体预防或治疗的疾病方面具有用处。这些化合物适用于治疗和预防可以受该受体影响的疾病，如代谢性疾病，特别是2型糖尿病。
• [EN] MLKL INHIBITORS<br/>[FR] INHIBITEURS MLKL
  申请人：NAT INSTITUTE OF BIOLOGICAL SCIENCES BEIJING

  公开号：WO2018157800A1

  公开（公告）日：2018-09-07

  Purine derivatives that inhibit cellular necroptosis and/or human MLKL, pharmaceutical compositions thereof, and methods of treating an MLKL-mediated disorder with an effective amount of the compound or composition. Said MLKL-mediated disorder is pathology associated necroptosis, including ischemia-reperfusion damage, neurodegeneration, and inflammatory diseases such as acute pancreatitis, multiple sclerosis, inflammatory bowel disease, and allergic colitis.

  嘌呤衍生物，用于抑制细胞坏死性凋亡和/或人类MLKL；包含该衍生物的药物组合物；以及使用有效量的该化合物或组合物治疗MLKL介导的疾病的方法。所述MLKL介导的疾病是与坏死性凋亡相关的病理学，包括缺血再灌注损伤、神经退行性疾病、以及诸如急性胰腺炎、多发性硬化症、炎症性肠病和过敏性结肠炎等炎症性疾病。
• [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。