63740-98-7Relevant articles and documents
Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships
Benturquia, Nadia,Chevillard, Lucie,Poiré, Christophe,Roussel, Olivier,Cohier, Camille,Declèves, Xavier,Laplanche, Jean-Louis,Etheve-Quelquejeu, Mélanie,Chen, Huixiong,Mégarbane, Bruno
, p. 891 - 901 (2018/07/13)
Rationale: The 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 methods: To study 3,4-methylenedioxypyrovalerone (MDPV; 3?mg/kg) and mephedrone (4-MMC; 30?mg/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 Emax modeling. Results: Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (p max (16.4 ± 5.5 versus 62.2 ± 14.2?μg/L, p 0 → ∞ (708 ± 91 versus 3316 ± 682?μg/L/min, p max model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC50, 0.043 versus 0.7?μmol/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.
Preparation method and applications of methylenedioxypyrovalerone artificial antigen
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Paragraph 0082; 0083; 0085, (2018/07/30)
The invention provides a methylenedioxypyrovalerone artificial antigen preparation method, which comprises: preparing hapten, wherein a bromobutane Grignard reagent is prepared in anhydrous diethyl ether by using bromobutane and a metal magnesium as raw materials, methylenedioxypyrovalerone with hydroxyl linked on a pyrrole ring is prepared by using the bromobutane Grignard reagent and 3,4-methylenedioxybenzonitrile as raw materials through carbonylation, bromination and pyrrole alcohol amination, and finally hapten containing long arm carboxyl is prepared by carrying out a reaction on succinic anhydride and the hydroxyl on the pyrrole ring; and coupling the hapten and protein to synthesize artificial antigen, wherein the hapten and bovine serum albumin are coupled through a carbodiimide-catalyzed active ester process to prepare the methylenedioxypyrovalerone artificial antigen. According to the present invention, the prepared methylenedioxypyrovalerone artificial antigen can be used for immunizing animals to obtain corresponding antibodies so as to be used for the researches on various methylenedioxypyrovalerone immunoassay and be used as the key raw material for the production ofmethylenedioxypyrovalerone immunochromatographic kits.
Differentiation of cyclic tertiary amine cathinone derivatives by product ion electron ionization mass spectrometry
Abiedalla, Younis,Abdel-Hay, Karim,Deruiter, Jack,Randall Clark
, p. 763 - 772 (2016/03/01)
Rationale A number of synthetic cathinones (aminoketones, 'bath salts') are tertiary amines containing a cyclic amino group, most commonly pyrrolidine. These totally synthetic compounds can be prepared in a number of regioisomeric designer modifications and many of these can yield isomeric major fragment ions in electron ionization mass spectrometry (EI-MS). Methods A series of regioisomeric cyclic tertiary amines were prepared and evaluated in EI-MS and MS/MS product ion experiments. The cyclic amines azetidine, pyrrolidine, piperidine and azepane were incorporated into a series of aminoketones related to the cathinone derivative drug of abuse known as MDPV. Deuterium labeling in both the cyclic amine and alkyl side chain allowed for the confirmation of the structure for the major product ions formed from the EI-MS iminium cation base peaks. Results These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the ring and side-chain portions of the structure. The small alkyl side chains favor ring fragmentation in the formation of the major product ions. The higher side-chain homologues appear to promote product ion formation by side-chain fragmentation. Both side-chain and ring fragmentation yield a mixture of product ions in the piperidine and azepane series. Conclusions Product ion fragmentation provides useful data for differentiation of cyclic tertiary amine iminium cations from cathinone derivative drugs of abuse. Regioisomeric iminium cations of equal mass yield characteristic product ions for the alkyl side-chain homologues of azetidine, pyrrolidine, piperidine and azepane cyclic amines.
Chiral resolution and absolute configuration of the enantiomers of the psychoactive designer drug 3,4-methylenedioxypyrovalerone
Suzuki, Masaki,Deschamps, Jeffrey R.,Jacobson, Arthur E.,Rice, Kenner C.
, p. 287 - 293 (2015/03/30)
Illicit rac-MDPV (3,4-methylenedioxypyrovalerone), manufactured in clandestine labs, has become widely abused for its cocaine-like stimulant properties. It has recently been found as one of the toxic materials in the so-called bath salts, producing, among other effects, psychosis and tachycardia in humans when introduced by any of the several routes of administration (e.g., intravenous, oral, etc.). 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 by 1H nuclear magnetic resonance and chiral high-performance liquid chromatography. The absolute stereochemistry of these enantiomers was determined by single-crystal X-ray diffraction studies. Chirality 27:287-293, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Continuous flow synthesis of ketones from carbon dioxide and organolithium or grignard reagents
Wu, Jie,Yang, Xiaoqing,He, Zhi,Mao, Xianwen,Hatton, T. Alan,Jamison, Timothy F.
supporting information, p. 8416 - 8420 (2014/08/18)
We describe an efficient continuous flow synthesis of ketones from CO 2 and organolithium or Grignard reagents that exhibits significant advantages over conventional batch conditions in suppressing undesired symmetric ketone and tertiary alcohol byproducts. We observed an unprecedented solvent-dependence of the organolithium reactivity, the key factor in governing selectivity during the flow process. A facile, telescoped three-step-one-flow process for the preparation of ketones in a modular fashion through the in-line generation of organometallic reagents is also established.
A new method of forming resin bound thioesters and their use as 'traceless' linkers in solid phase synthesis
May, Peter J.,Bradley, Mark,Harrowven, David C.,Pallin, David
, p. 1627 - 1630 (2007/10/03)
Resin bound thioesters can be prepared by heating thioamides in aqueous DMF with Merrifield resin in the presence of sodium iodide. These thioamides can be cleaved to give alcohols, ketones and lactones by a variety of methods. (C) 2000 Elsevier Science Ltd.
