1-(1,3-苯并二氧杂环戊-5-基)-2-(1-吡咯烷基)-1-戊酮 | 687603-66-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(1,3-苯并二氧杂环戊-5-基)-2-(1-吡咯烷基)-1-戊酮
• 中文别名: 亚甲基二氧吡咯戊酮
• 英文名称: MDPV
• 英文别名: 3,4-methylenedioxypyrovalerone；1-(1,3-benzodioxol-5-yl)-2-pyrrolidin-1-ylpentan-1-one；Methylenedioxypyrovalerone
• CAS: 687603-66-3
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: SYHGEUNFJIGTRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

MDPV的代谢在体外使用人肝微粒体和S9细胞组分进行了评估，以研究CYP450 I相和尿苷5'-二磷酸葡萄糖醛酸转移酶（UGT）以及硫酸转移酶（SULT）II相代谢。随后，通过液/液萃取得到的代谢物使用气相色谱/质谱（GC/MS）以三甲基硅（TMS）衍生物的形式进行分析。代谢物的结构通过使用液相色谱/四级飞行时间（LC/QTOF）质谱仪进行精确质量测量进一步确认。研究表明，MDPV的主要代谢物是儿茶酚和对甲氧基儿茶酚，它们进而被硫酸化和葡萄糖醛酸化。

The metabolism of methylenedioxypyrovalerone (MDPV) was evaluated in vitro using human liver microsomes and S9 cellular fractions for CYP450 phase I and uridine 5'-diphosphoglucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II metabolism studies. The resulting metabolites were subsequently liquid/liquid extracted and analyzed using gas chromatography/mass spectrometry (GC/MS) as trimethylsilyl (TMS) derivatives. The structures of the metabolites were further confirmed by accurate mass measurement using a liquid chromatography/quadrupole time-of-flight (LC/QTOF) mass spectrometer. The studies demonstrated that the main metabolites of MDPV are catechol and methyl catechol pyrovalerone, which are in turn sulfated and glucuronated. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

征兆和症状/ 用户报告称，他们每回合服用MDPV不超过5毫克，并且有用户对MDPV产生渴望的报告。MDPV的急性副作用包括心动过速、高血压、血管收缩和出汗。主观效果持续大约3到4小时，副作用在服用后总共持续6到8小时。对刺激性药物不耐受的用户服用较高剂量的MDPV后，会引起剧烈、持久的恐慌发作。用户报告称，在睡眠剥夺和在使用较高剂量或更频繁的剂量间隔使用后，会出现精神病发作并成瘾。当MDPV溶解时，其效力会降低。

/SIGNS AND SYMPTOMS/ Users of MDPV anecdotally report that they take 5 mg or less per session and there have been reports of cravings for MDPV by users. The acute side effects of MDPV include tachycardia, hypertension, vasoconstriction, and sweating. The duration of the subjective effects is about 3 to 4 hours and the side effects continuing a total of 6 to 8 hours after administration. Higher doses of MDPV have caused intense, prolonged panic attacks in stimulant-intolerant users. Users have reported bouts of psychosis induced by sleep deprivation and becoming addicted after using higher doses or using at more frequent dosing intervals. MDPV loses potency when it is put into solution.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/监控/ 2011年2月1日，针对多篇新闻报道，密歇根州社区健康部（MDCH）联系了密歇根儿童医院毒物控制中心（PCC），询问有关该州因使用作为“浴盐”销售的娱乐设计药物而导致的疾病报告。与传统的用于浸泡和清洁的包装和销售的化妆品浴盐不同，作为“浴盐”销售的药物对于沐浴没有合法用途，且旨在滥用。这些产品可能含有刺激化合物，如3,4-亚甲二氧基吡咯戊酮（MDPV）或4-甲基甲卡西酮（喵喵粉）。PCC告诉MDCH，当天早些时候，PCC了解到有多人因心血管和神经急性中毒迹象到访了马凯特县的当地急诊科（ED）。本报告总结了对35名摄入、吸入或注射“浴盐”并在此期间访问密歇根ED的人的后续调查。在这35名患者中，毒性最常见的体征和症状是激动（23名患者[66%]）、心动过速（22名[63%]）和妄想/幻觉（14名[40%]）。17名患者被住院治疗，一名患者在到达ED时已经死亡。公共卫生机构、卫生保健提供者、毒物控制中心和执法机构的协调努力使这一新兴健康问题得到迅速识别。解决这一问题需要执行紧急公共卫生命令，将有毒的“浴盐”从市场上清除。密歇根州的这一经验对其他遇到类似问题的美国地区可能具有借鉴意义。

/SURVEILLANCE/ On February 1, 2011, in response to multiple news reports, the Michigan Department of Community Health (MDCH) contacted the Children's Hospital of Michigan Poison Control Center (PCC) regarding any reports of illness in the state caused by the use of recreational designer drugs sold as "bath salts." Unlike traditional cosmetic bath salts, which are packaged and sold for adding to bath water for soaking and cleaning, the drugs sold as "bath salts" have no legitimate use for bathing and are intended for substance abuse. These products can contain stimulant compounds such as 3,4-methylenedioxypyrovalerone (MDPV) or 4-methylmethcathinone (mephedrone). The PCC told MDCH that, earlier in the day, the PCC had learned that numerous persons had visited the local emergency department (ED) in Marquette County with cardiovascular and neurologic signs of acute intoxication. This report summarizes the subsequent investigation, which identified 35 persons who had ingested, inhaled, or injected "bath salts" and visited a Michigan ED during November 13, 2010--March 31, 2011. Among the 35 patients, the most common signs and symptoms of toxicity were agitation (23 patients [66%]), tachycardia (22 [63%]), and delusions/hallucinations (14 [40%]). Seventeen patients were hospitalized, and one was dead upon arrival at the ED. The coordinated efforts of public health agencies, health-care providers, poison control centers, and law enforcement agencies enabled rapid identification of this emerging health problem. Mitigation of the problem required the execution of an emergency public health order to remove the toxic "bath salts" from the marketplace. Lessons from the Michigan experience could have relevance to other areas of the United States experiencing similar problems.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  1-(1,3-苯并二氧杂环戊-5-基)-2-(1-吡咯烷基)-1-戊酮 在 盐酸 作用下， 以 异丙醇 为溶剂， 以22.2 g的产率得到1-(3,4-亚甲基二氧苯基)-2-吡咯烷-1-基戊酮盐酸盐
  参考文献：
  名称：

  精神活性“设计药物” 3,4-亚甲基二氧基吡咯烷酮对映体的手性拆分和绝对构型

  摘要：

  在秘密实验室生产的Illicit rac ‐MDPV（3,4-亚甲基二氧基吡咯烷酮）因其具有类似可卡因的刺激性而被广泛滥用。最近，它被发现为所谓的“沐浴盐”中的一种有毒物质，当通过多种给药途径（例如静脉内，口服等）引入时，会在人类中引起精神病和心动过速等其他症状。 ）。这种“设计药物”的相当大的毒性可能存在于外消旋体的一种对映异构体中。为了获得足够数量的rac -MDPV对映体以确定其活性，我们改进了rac的已知合成方法-MDPV并发现化学拆分剂（+）-和（-）-2'-溴四乙酸，通过1 H核磁共振和手性高效液相色谱测定，MDPV对映体的对映体过量> 96％。这些对映体的绝对立体化学是通过单晶X射线衍射研究确定的。手性27：287-293，2015。2015年出版。本文是美国政府的工作，在美国属于公共领域。

  DOI：

  10.1002/chir.22423
• 作为产物：
  描述：

  1-(苯并[d][1,3]二氧代l-5-基)-1-戊酮 在 溴 作用下， 以 乙醚 、 氯仿 为溶剂， 生成 1-(1,3-苯并二氧杂环戊-5-基)-2-(1-吡咯烷基)-1-戊酮
  参考文献：
  名称：

  精神活性“设计药物” 3,4-亚甲基二氧基吡咯烷酮对映体的手性拆分和绝对构型

  摘要：

  在秘密实验室生产的Illicit rac ‐MDPV（3,4-亚甲基二氧基吡咯烷酮）因其具有类似可卡因的刺激性而被广泛滥用。最近，它被发现为所谓的“沐浴盐”中的一种有毒物质，当通过多种给药途径（例如静脉内，口服等）引入时，会在人类中引起精神病和心动过速等其他症状。 ）。这种“设计药物”的相当大的毒性可能存在于外消旋体的一种对映异构体中。为了获得足够数量的rac -MDPV对映体以确定其活性，我们改进了rac的已知合成方法-MDPV并发现化学拆分剂（+）-和（-）-2'-溴四乙酸，通过1 H核磁共振和手性高效液相色谱测定，MDPV对映体的对映体过量> 96％。这些对映体的绝对立体化学是通过单晶X射线衍射研究确定的。手性27：287-293，2015。2015年出版。本文是美国政府的工作，在美国属于公共领域。

  DOI：

  10.1002/chir.22423

文献信息

• Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography
  作者：Gabriela Kucerova、Kveta Kalikova、Eva Tesarova

  DOI：10.1002/chir.22701

  日期：2017.6

  cellulose‐based chiral stationary phase were achieved particularly with propane‐2‐ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose‐based chiral stationary phase. The complementary enantioselectivity of the cellulose‐ and amylose‐based chiral stationary phases allows separation

  使用一组52种分析物在超临界流体色谱中评估了两种基于多糖的手性固定相对手性结构多样的生物活性化合物的对映选择性。固定在2.5μm二氧化硅颗粒上的手性选择剂是纤维素或直链淀粉的三（3,5-二甲基苯基carmabate）衍生物。监测了多糖主链，不同的有机改性剂和不同的流动相添加剂对保留和对映体分离的影响。对于大多数化合物，发现了快速基线对映体分离的条件。纤维素基手性固定相的基线和部分对映体分离的成功率分别为51.9％和15.4％。使用基于直链淀粉的手性固定相，我们获得了76。被测化合物的基线对映体分离率为9％，部分对映体分离率为9.6％。尤其是使用丙烷-2-醇以及异丙胺和三氟乙酸的混合物作为有机改性剂和CO添加剂时，在基于纤维素的手性固定相上获得了最佳结果2个。在基于直链淀粉的手性固定相上，优选甲醇和碱性添加剂异丙胺。纤维素和直链淀粉基手性固定相的互补对映选择性可分离大多数经测试的结构不同的化
• Successful use of a novel lux® i‐Amylose‐1 chiral column for enantioseparation of “legal highs” by HPLC
  作者：Kian Kadkhodaei、Marlene Kadisch、Martin G. Schmid

  DOI：10.1002/chir.23135

  日期：2020.1

  enantiomers may differ in their pharmacological effect. The aim of this study was to test a novel HPLC column for the enantioseparation of a set of 112 NPS coming from different chemical groups and collected by internet purchases during the years 2010–2018. The CSP, namely Lux® 5 μm i‐Amylose‐1, LC Column 250 x 4.6 mm, was run in normal phase mode under isocratic conditions, UV detection was performed

  这些术语背后隐藏着浴盐，熏蒸剂，清洁剂和空气清新剂，这些物质被算作“合法上限”。这些花哨的名字被用来装扮成合法的无害化合物，以规避市场营销的法律法规并增加销量。除了合成的经典非法药物（如苯丙胺，可卡因和摇头丸）以外，这些化合物的贸易（也称为新型精神活性物质（NPS））在当今并不罕见。在许多国家，NPS仍然不受药物管制。其中，有具有手性中心的兴奋剂，例如新的苯丙胺衍生物或卡西酮。关于两种可能的对映异构体的药理作用可能不同的事实知之甚少。这项研究的目的是测试一种新颖的HPLC色谱柱，该色谱柱用于对映分离2010年至2018年间通过互联网购买的来自不同化学族的112种NPS。CSP，即Lux®5μmi-Amylose-1，LC色谱柱250 x 4.6 mm，在等度条件下以正相模式运行，在245 nm和230 nm处进行UV检测，进样量为10μl，流速为为1毫升/分钟。使用由正己烷/异丙醇/二乙胺（90：10：0
• IMMUNOASSAY FOR PYRROLIDINOPHENONES
  申请人：RANDOX LABORATORIES LIMITED

  公开号：US20160097783A1

  公开（公告）日：2016-04-07

  The current invention provides an improved immunoassay for the detection and determination of pyrrolidinophenone based designer drugs in hair and biological fluids (urine, blood, and oral fluid). The generic immunoassay is underpinned by novel, sub-family-specific antibodies, which display surprising sensitivity. The invention further describes substrates comprising an antibody that is specific to compounds of the pyrrolidinophenone family. Also described are the novel immunogens from which the antibodies are derived and kits incorporating the antibodies of the current invention.

  该发明提供了一种改进的免疫测定方法，用于检测和测定基于哌哆利啶酮类设计药物在头发和生物液体（尿液、血液和口腔液）中的含量。通用的免疫测定方法基于新颖的、亚家族特异性抗体，显示出惊人的灵敏度。该发明进一步描述了包含特异于哌哆利啶酮类化合物的抗体的底物。还描述了从中获得抗体的新颖免疫原以及包含本发明抗体的试剂盒。
• Immunoassay for Phenethylamines of the 2C and DO Sub-Families
  申请人：Randox Laboratories Limited

  公开号：US20150038366A1

  公开（公告）日：2015-02-05

  Immunoassay methods and their requisite components for the detection and determination of phenethylamines of the 2C and DO sub-families are described.

  描述了用于检测和测定2C和DO亚家族苯乙胺的免疫分析方法及其必要组成部分。
• IMPROVED IMMUNOASSAY FOR PYRROLIDINOPHENONES
  申请人：Randox Laboratories Ltd.

  公开号：EP3002592A1

  公开（公告）日：2016-04-06

  The current invention provides an improved immunoassay for the detection and determination of pyrrolidinophenone based designer drugs in biological fluids (Urine, Blood, Oral fluid and Hair). The generic immunoassay is underpinned by novel, subfamily-specific antibodies which display surprising sensitivity. The invention further describes substrates comprising an antibody that is specific to compounds of the pyrrolidinophenone family. Also described are the novel immunogens from which the antibodies are derived and kits incorporating the antibodies of the current invention.

  本发明提供了一种改进的免疫测定法，用于检测和测定生物液体（尿液、血液、口服液和毛发）中的吡咯烷酮类特效药。这种通用免疫分析法以新型亚族特异性抗体为基础，显示出惊人的灵敏度。本发明进一步描述了包含对吡咯烷酮家族化合物具有特异性的抗体的底物。本发明还描述了衍生抗体的新型免疫原和包含本发明抗体的试剂盒。