5-丁烷-2-基-5-丙-2-烯基-1,3-二嗪农-2,4,6-三酮 | 115-44-6

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-丁烷-2-基-5-丙-2-烯基-1,3-二嗪农-2,4,6-三酮
• 中文别名: 他布比妥CIII；烯丁巴比妥；丙烯丁比妥；丁烯丙巴比妥；他布比妥
• 英文名称: talbutal
• 英文别名: Lotusate；5-allyl-5-sec-butyl-pyrimidine-2,4,6-trione；5-allyl-5-sec-butyl-barbituric acid；5-Allyl-5-sec-butyl-barbitursaeure；5-Allyl-5--barbitursaeure；5-butan-2-yl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
• CAS: 115-44-6
• 化学式: C₁₁H₁₆N₂O₃
• mdl: MFCD00868021
• 分子量: 224.26
• InChiKey: BJVVMKUXKQHWJK-UHFFFAOYSA-N

物化性质

• 熔点：
  108-110°
• 沸点：
  365.66°C (rough estimate)
• 密度：
  1.1672 (rough estimate)
• 溶解度：
  可溶于氯仿（略微加热）、甲醇（略微加热）
• 颜色/状态：
  CRYSTALS FROM WATER OR DIL ALCOHOL
• 气味：
  MAY HAVE SLIGHT ODOR OF CARAMEL
• 味道：
  SLIGHTLY BITTER TASTE
• 解离常数：
  PKA: ABOUT 9.4
• 保留指数：
  1689;1689;1704;1677;1701

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  75.3
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

大多数巴比妥类药物在体内转化为无活性的代谢物。生物转化的主要部位是肝脏。氧化巴比妥类药物仅由肝脏转化；硫代巴比妥类药物在其他组织中可能只有少量转化，尤其是肾脏和大脑... /巴比妥类药物/

MOST BARBITURATES ARE TRANSFORMED IN BODY TO INACTIVE METABOLITES. PRINCIPAL SITE OF BIOTRANSFORMATION IS LIVER. OXYBARBITURATES ARE TRANSFORMED ONLY BY LIVER; THIOBARBITURATES MAY BE TRANSFORMED TO SMALL EXTENT IN OTHER TISSUES, ESP KIDNEY & BRAIN ... /BARBITURATES/

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏生物转化，主要由肝脏微粒体酶系完成。/巴比妥类药物/

Hepatic biotransformation, primarily by the hepatic microsomal enzyme system. /Barbiturates/

来源:Hazardous Substances Data Bank (HSDB)

代谢

除去了较不易溶于脂肪的阿普罗巴比妥和苯巴比妥外，几乎所有的巴比妥类药物在肝脏都会经历完全的代谢和/或结合，然后才通过肾脏排出体外。C5位置上自由基的氧化是最重要的生物转化，负责终止其生物活性。氧化会导致醇、酮、酚或羧酸的形成，这些物质可能会以原形或作为葡萄糖醛酸结合物出现在尿液中。在某些情况下（例如，苯巴比妥），N-葡萄糖苷化是一个重要的代谢途径。其他生物转化包括N-羟基化、硫代巴比妥向氧化巴比妥的脱硫、巴比妥酸环的开环以及N-烷基巴比妥向活性代谢物（例如，甲戊巴比妥向苯巴比妥）的N-脱烷基化。

With the exception of the less lipid-soluble aprobarbital and phenobarbital, nearly complete metabolism and/or conjugation of barbiturates in the liver precedes their renal excretion. The oxidation of radicals at C5 is the most important biotransformation responsible for termination of biological activity. Oxidation results in the formation of alcohols, kentones, phenols, or carboxylic acids, which may appear in the urine as such or as glucuronic acid conjugates. In some instances (e.g., phenobarbital), N-glucosylation is an important metabolic pathway. Other biotransformations include N-hydroxylation, desulfuration of thiobarbiturates to oxybarbiturates, opening of the barbituric acid ring, and N-dealkylation of N-alkylbarbiturates to active metabolites (e.g., mephobarbital to phenobarbital).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

巴比妥类药物可能会降低口服抗凝剂的低凝血酶原效果。巴比妥类药物与肾上腺皮质类固醇相互作用，导致类固醇的血清水平降低和系统性效果下降；可能的机制是诱导微粒体酶活性。

... BARBITURATES MAY CAUSE DECR HYPOPROTHROMBINEMIC EFFECT OF ORAL ANTICOAGULANTS. ... BARBITURATES INTERACT WITH ADRENAL CORTICOSTEROIDS TO CAUSE REDUCED SERUM LEVELS & DECR SYSTEMIC EFFECTS OF STEROIDS; PROBABLE MECHANISM IS INDUCTION OF MICROSOMAL ACTIVITY. /BARBITURATES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

减少强力霉素（盐酸多西环素）的血清水平...当同时给予巴比妥类药物时报告；可能的机制是诱导微粒体酶活性。降低灰黄霉素的血清水平...注意到...当同时给予巴比妥类药物时，氯丙嗪可能会更快地被代谢。/巴比妥类药物/

DECR SERUM LEVELS OF DOXYCYCLINE (VIBRAMYCIN) ... REPORTED WHEN BARBITURATE ... GIVEN CONCURRENTLY; PROBABLE MECHANISM IS INDUCTION OF MICROSOMAL ENZYME ACTIVITY. DECR SERUM LEVELS OF GRISEOFULVIN ... NOTED ... CHLORPROMAZINE MAY BE MORE RAPIDLY METABOLIZED WHEN BARBITURATES ... GIVEN CONCURRENTLY. /BARBITURATES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

单胺氧化酶抑制剂增强巴比妥类药物的作用... /巴比妥类药物/

MONOAMINE OXIDASE INHIBITORS POTENTIATE ACTION OF BARBITURATES ... /BARBITURATES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

致命血液浓度.../水平/...可能是...1毫克/100毫升，对于中效和短效巴比妥类药物；如果还使用了其他抑制类药物或酒精，致命浓度可能会更低。/巴比妥类药物，短效和中效/

LETHAL BLOOD ... /LEVEL/ ... MAY BE ... 1 MG/100 ML FOR INTERMEDIATE- & SHORT-ACTING BARBITURATES; IF OTHER DEPRESSANT DRUGS OR ALC ARE ALSO PRESENT, LETHAL CONCN MAY BE EVEN LOWER. /BARBITURATES, SHORT & INTERMEDIATE ACTING/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

治疗：稳定化处理：呼吸骤停是早期死亡的主要原因。首先评估气道的通畅性和通气的充足性。适当的纠正措施包括补充氧气、头部倾斜-下巴提升、插管和辅助通气。对于低血压的患者，建立静脉输液线并给予乳酸林格氏液至2升的液体挑战。心脏心律失常很少见，但有过报道。确保给所有精神状态低落的病人给予葡萄糖、纳洛酮和硫胺素。/巴比妥类药物/

TREATMENT: Stabilization: Respiratory arrest is the major cause of early death. Assess the patency of the airway and the adequacy of ventilation first. Appropriate corrective measures include supplemental oxygen, head tilt-chin lift, intubation, and assisted ventilation. Establish an iv line with Ringer's lactate and give a fluid challenge up to 2 l for patients who are hypotensive. Cardiac dysrhythmias are rare but were reported. ... Be sure to give glucose, naloxone, and thiamine to all patients with depressed mental status. /Barbiturates/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

没有任何不可渗透的屏障可以阻止巴比妥类药物在体内的扩散...在摄入大剂量后，可能会在乳汁中发现少量...它们容易穿过胎盘屏障，并且在注射短效巴比妥类药物后几分钟内，胎儿血液中的浓度就会接近母体静脉血中的浓度。/巴比妥类药物/

THERE EXISTS NO IMPENETRABLE BARRIER TO DIFFUSION OF BARBITURATES IN BODY ... SMALL AMT ... MAY APPEAR IN MILK AFTER INGESTION OF LARGE DOSES. ... READILY CROSS PLACENTAL BARRIER, &, WITHIN FEW MIN AFTER INJECTION OF SHORT-... ACTING BARBITURATE, CONCN IN FETAL BLOOD APPROACHES THAT IN MATERNAL VENOUS BLOOD. /BARBITURATES/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

影响巴比妥类药物分布和命运的三个最重要因素是脂溶性、蛋白质结合和电离程度。脂溶性越高的化合物通常是短效剂，它们倾向于更快地通过代谢降解，并且几乎完全被肾小管重吸收。

THREE MOST IMPORTANT FACTORS AFFECTING DISTRIBUTION & FATE OF BARBITURATES ARE LIPID SOLUBILITY ... PROTEIN BINDING, & EXTENT OF IONIZATION. ... THE MORE HIGHLY LIPID-SOL COMPD ARE SHORT-ACTING AGENTS... THEY TEND TO BE MORE RAPIDLY DEGRADED METABOLICALLY & ARE ALMOST COMPLETELY REABSORBED BY RENAL TUBULE. /BARBITURATES/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

用于镇静催眠时，巴比妥类药物通常通过口服给药。这样剂量的药物会迅速且可能完全被吸收；钠盐的吸收速度比相应的自由酸快，尤其是从液体配方中。作用开始的时间因药物和配方不同而异，通常在10到60分钟之间，食物在胃中的存在会延迟其起效。/巴比妥类药物/

For sedative hypnotic use, the barbiturates are usually administered orally. Such doses are rapidly and probably completely absorbed; sodium salts are absorbed more rapidly than the corresponding free acids, especially from liquid formulations. The onset of action varies from 10 to 60 min, depending upon the agent and the formulation, and is delayed by the presence of food in stomach. /Barbiturates/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

巴比妥类药物分布广泛，容易穿过胎盘。与血浆蛋白的结合是脂溶性的一个功能，对于硫喷妥来说是最高的，其结合程度达到65%或更多。高脂溶性的巴比妥类药物，尤其是用于诱导麻醉的那些，在静脉注射后会发生再分布。被较少血管组织的摄取，特别是肌肉和脂肪，导致血浆和大脑中巴比妥类药物浓度的下降。

Barbiturates are distributed widely and readily cross the placenta. Binding to plasma proteins is a function of lipid solubility and is greatest for thiopental, which is bound to the extent of 65% or more. The highly lipid soluble barbiturates, led by those used to induce anesthesia, undergo redistribution after intravenous injection. Uptake into less vascular tissue, especially muscle and fat, leads to a decline in the concentration of barbiturate in the plasma and brain.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

消除/% 未改变：肾/微量

Elimination/% excreted unchanged: renal/trace

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 海关编码：
  2933540000
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 3249

制备方法与用途

类别：有毒物品
毒性分级：高毒
急性毒性：口服-大鼠 LD50：57.5 毫克/公斤；口服-豚鼠 LD50：56 毫克/公斤
可燃性危险特性：易燃，燃烧时产生有毒氮氧化物烟雾
储运特性：库房应保持通风、低温和干燥，并与食品原料分开存放
灭火剂：干粉、泡沫、砂土、二氧化碳或雾状水

反应信息

• 作为反应物：
  描述：

  5-丁烷-2-基-5-丙-2-烯基-1,3-二嗪农-2,4,6-三酮 在 氨 作用下， 生成 Allyl-(1-methylpropyl)-acetamid
  参考文献：
  名称：

  Hydrolysis of 5,5-Disubstituted Barbituric Acids

  摘要：

  DOI：

  10.1021/jo01060a048
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 sodium ethanolate 、 尿素 作用下， 生成 5-丁烷-2-基-5-丙-2-烯基-1,3-二嗪农-2,4,6-三酮
  参考文献：
  名称：

  CH138440

  摘要：

  公开号：

文献信息

• [EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
  申请人：GALLEON PHARMACEUTICALS INC

  公开号：WO2009151744A1

  公开（公告）日：2009-12-17

  The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.

  本发明涉及基于巯基和S-亚硝基巯基的SNO化合物及其衍生物，以及它们在治疗正常呼吸控制缺失方面的用途，包括治疗与睡眠、肥胖、某些药物和其他医疗状况相关的呼吸暂停和低通气。
• Chemical Compounds
  申请人：Brown Alan Daniel

  公开号：US20120010182A1

  公开（公告）日：2012-01-12

  The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new sulfonamide Nav1.7 inhibitors of formula (I): or pharmaceutically acceptable salts thereof, wherein Z 1 , R a , R b , R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.

  该发明涉及磺胺衍生物，其在医学上的应用，含有它们的组合物，其制备方法以及用于这些方法的中间体。 更具体地，该发明涉及公式（I）的新磺胺基Nav1.7抑制剂： 或其药学上可接受的盐，其中Z 1 ，R a ，R b ，R 1 ，R 2 ，R 3 ，R 4 和R 5 如描述中所定义。 Nav 1.7抑制剂在治疗各种疾病，特别是疼痛方面具有潜在用途。
• [EN] COMBINATIONS COMPRISING ALPHA-2-DELTA LIGANDS<br/>[FR] COMBINAISONS CONTENANT DES LIGANDS DE ALPHA-2-DELTA
  申请人：PFIZER LTD

  公开号：WO2005092318A1

  公开（公告）日：2005-10-06

  The instant invention relates to a combination, particularly a synergistic combination, of an alpha-2-delta ligand and an atypical antipsychotic, and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and their use in the treatment of pain, particularly neuropathic pain.

  这项即时发明涉及一种组合，特别是α-2-δ配体和非典型抗精神病药物的协同组合，以及其药用盐、药物组合物及其在治疗疼痛，特别是神经病痛中的应用。
• PYRROLOPYRAZINE-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
  申请人：Hadida Ruah Sara Sabina

  公开号：US20120196869A1

  公开（公告）日：2012-08-02

  The invention relates to pyrrolopyrazine-spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  这项发明涉及对离子通道具有抑制作用的吡咯吡嘧啶-螺环哌啶酰胺化合物。该发明还提供了包括该发明化合物的药学上可接受的组合物，以及使用这些组合物治疗各种疾病的方法。
• [EN] DEUTERATED PYRIDONE AMIDES AND PRODRUGS THEREOF AS MODULATORS OF SODIUM CHANNELS<br/>[FR] AMIDES DE PYRIDONE DEUTÉRÉS ET LEURS PROMÉDICAMENTS UTILISÉS EN TANT QUE MODULATEURS DE CANAUX SODIQUES
  申请人：VERTEX PHARMA

  公开号：WO2018213426A1

  公开（公告）日：2018-11-22

  Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. The compounds have the formula (I) wherein R is H or CH2OPO(OH)2. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

  提供了作为钠通道抑制剂的化合物及其药用盐。这些化合物的化学式为（I），其中R为H或CH2OPO(OH)2。还提供了包含这些化合物或药用盐的药物组合物，以及使用这些化合物、药用盐和药物组合物治疗各种疾病，包括疼痛的方法。

表征谱图