1-(3,4-亚甲基二氧苯基)-2-吡咯烷-1-基戊酮盐酸盐 | 24622-62-6

• 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-(3,4-亚甲基二氧苯基)-2-吡咯烷-1-基戊酮盐酸盐
• 英文名称: 3,4-methylenedioxypyrovalerone hydrochloride
• 英文别名: MDPV；(±)-3,4-methylenedioxypyrovalerone hydrochloride；MDPV hydrochloride；MDPV HCl；Methylenedioxypyrovalerone hydrochloride；1-(1,3-benzodioxol-5-yl)-2-pyrrolidin-1-ylpentan-1-one;hydrochloride
• CAS: 24622-62-6
• 化学式: C₁₆H₂₁NO₃*ClH
• 分子量: 311.809
• InChiKey: PYQZNWFQAMFAMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  21
• 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：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3,4-亚甲基二氧苯基)-2-吡咯烷-1-基戊酮盐酸盐 在 sodium carbonate 作用下， 以 乙醚 、 水 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
• 作为产物：
  描述：

  胡椒环 在 溴 、 四氯化锡 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 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：

  Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships

  摘要：

  RationaleThe use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated.Objective and methodsTo study 3,4-methylenedioxypyrovalerone (MDPV; 3mg/kg) and mephedrone (4-MMC; 30mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal E-max modeling.ResultsLocomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (p<0.001) and 4-MMC (p<0.01) alone. The pharmacokinetic profile of MDPV, but not 4-MMC, was significantly modified with the combination resulting in decreases in C-max (16.45.5 versus 62.2 +/- 14.2g/L, p<0.05) and AUC(0) (708 +/- 91 versus 3316 +/- 682g/L/min, p<0.01) and increases in V/F (582.6 +/- 136.8 versus 115.9 +/- 42.7L/kg, p<0.05) and Cl/F (4.6 +/- 0.7 versus 1.2 +/- 0.4L/kg/min, p<0.01) in comparison to MDPV alone. The sigmoidal E-max model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC50, 0.043 versus 0.7mol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3.Conclusion An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.

  DOI：

  10.1007/s00213-018-4962-0

文献信息

• IMMUNOASSAY FOR PYRROLIDINOPHENONES
  申请人：Randox Laboratories Limited

  公开号：US20130210167A1

  公开（公告）日：2013-08-15

  The invention describes antibodies that bind molecules of the pyrrolidinophenone class of synthetic drugs. The antibodies are derived from novel chemical intermediates, haptens and immunogens and are used in methods and kits to detect and quantify pyrrolidinophenones.

  该发明描述了能够结合合成药物吡咯烷基苯酮类分子的抗体。这些抗体来源于新型化学中间体、半抗原和免疫原，并用于检测和定量吡咯烷基苯酮的方法和试剂盒中。
• Immunoassay for pyrrolidinophenones
  申请人：Randox Laboratories Ltd.

  公开号：EP2626358B1

  公开（公告）日：2015-09-02
• “Deconstruction” of the Abused Synthetic Cathinone Methylenedioxypyrovalerone (MDPV) and an Examination of Effects at the Human Dopamine Transporter
  作者：Renata Kolanos、Ernesto Solis、Farhana Sakloth、Louis J. De Felice、Richard A. Glennon

  DOI：10.1021/cn4001236

  日期：2013.12.18

  Synthetic cathinones, beta-keto analogues of amphetamine (or, more correctly, of phenylalkylamines), represent a new and growing class of abused substances. Several such analogues have been demonstrated to act as dopamine (DA) releasing agents. Methylenedioxypyrovalerone (MDPV) was the first synthetic cathinone shown to act as a cocaine-like DA reuptake inhibitor. MDPV and seven deconstructed analogues were examined to determine which of MDPV's structural features account(s) for uptake inhibition. In voltage-clamped (-60 mV) Xenopus oocytes transfected with the human DA transporter (hDAT), all analogues elicited inhibitor-like behavior shown as hDAT-mediated outward currents. Using hDAT-expressing mammalian cells we determined the affinities of MDPV and its analogues to inhibit uptake of [H-3]DA by hDAT that varied over a broad range (IC50 values ca. 135 to >25 000 nM). The methylenedioxy group of MDPV made a minimal contribution to affinity, the carbonyl group and a tertiary amine are more important, and the extended a-alkyl group seems most important. Either a tertiary amine, or the extended a-alkyl group (but not both), are required for the potent nature of MDPV as an hDAT inhibitor.
• Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships
  作者：Nadia Benturquia、Lucie Chevillard、Christophe Poiré、Olivier Roussel、Camille Cohier、Xavier Declèves、Jean-Louis Laplanche、Mélanie Etheve-Quelquejeu、Huixiong Chen、Bruno Mégarbane

  DOI：10.1007/s00213-018-4962-0

  日期：2019.3

  RationaleThe use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated.Objective and methodsTo study 3,4-methylenedioxypyrovalerone (MDPV; 3mg/kg) and mephedrone (4-MMC; 30mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal E-max modeling.ResultsLocomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (p<0.001) and 4-MMC (p<0.01) alone. The pharmacokinetic profile of MDPV, but not 4-MMC, was significantly modified with the combination resulting in decreases in C-max (16.45.5 versus 62.2 +/- 14.2g/L, p<0.05) and AUC(0) (708 +/- 91 versus 3316 +/- 682g/L/min, p<0.01) and increases in V/F (582.6 +/- 136.8 versus 115.9 +/- 42.7L/kg, p<0.05) and Cl/F (4.6 +/- 0.7 versus 1.2 +/- 0.4L/kg/min, p<0.01) in comparison to MDPV alone. The sigmoidal E-max model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC50, 0.043 versus 0.7mol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3.Conclusion An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.
• Chiral Resolution and Absolute Configuration of the Enantiomers of the Psychoactive “Designer Drug” 3,4-Methylenedioxypyrovalerone
  作者：Masaki Suzuki、Jeffrey R. Deschamps、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1002/chir.22423

  日期：2015.4

  ). The considerable toxicity of this “designer drug” probably resides in one of the enantiomers of the racemate. In order to obtain a sufficient amount of the enantiomers of rac‐MDPV to determine their activity, we improved the known synthesis of rac‐MDPV and found chemical resolving agents, (+)‐ and (–)‐2’‐bromotetranilic acid, that gave the MDPV enantiomers in >96% enantiomeric excess as determined

  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。