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Simon P. Elliott Simon D. Brandt Sally Freeman Roland P. Archer 《Drug testing and analysis》2013,5(3):196-202
5‐(2‐Aminopropyl)indole (5‐IT) and 3‐(2‐aminopropyl)indole (α‐methyltryptamine, AMT) are isomeric substances and their differentiation can be a challenge under routine analytical conditions, especially when reference material is unavailable. 5‐IT represents a very recent addition to the battery of new psychoactive substances that are commercially available from online retailers. This report illustrates how subtle differences observed under mass spectral and UV conditions can help to facilitate the differentiation between the two isomers. Analyses included 1 H and 13C NMR, GC‐EI/CI ion trap MS, applications of several U/HPLC‐DAD and HPLC‐MS methods. Investigations currently underway also highlight the confirmation that AMT was detected in a number of fatal intoxications. These findings also demonstrate that there is a potential risk of misidentification when dealing with both substances. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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Simon D. Brandt Harry R. Sumnall Fiona Measham Jon Cole 《Drug testing and analysis》2010,2(8):377-382
In the UK, mephedrone and other so‐called ‘legal high’ derivatives have recently been classified as Class B, Schedule I under the Misuse of Drugs Act 1971. Since then, alternative products have been advertised on a number of websites. In order to obtain an immediate snapshot of the situation, 24 products were purchased online from 18 UK‐based websites over a period of 6 weeks following the ban in April 2010. Qualitative analyses were carried out by gas chromatography ion trap mass spectrometry using electron‐ and chemical ionization modes, nuclear magnetic resonance spectroscopy, and comparison with reference standards. Overall, the purchased products consisted of single cathinones or cathinone mixtures including mephedrone, butylone, 4‐methyl‐N‐ethylcathinone, flephedrone (4‐fluoromethcathinone) and MDPV (3,4‐methylenedioxypyrovalerone), respectively. Benzocaine, caffeine, lidocaine, and procaine were also detected. The emphasis was placed on ‘Energy 1’ (NRG‐1), a product advertised as a legal replacement for mephedrone‐type derivatives usually claiming to contain naphyrone (naphthylpyrovalerone, O‐2482). It was found that 70% of NRG‐1 and NRG‐2 products appeared to contain a mixture of cathinones banned in April 2010 and rebranded as ‘new’ legal highs, rather than legal chemicals such as naphyrone as claimed by the retailers. Only one out of 13 NRG‐1 samples appeared to show analytical data consistent with naphyrone. These findings also suggest that both consumers and online sellers (unlike manufacturers and wholesalers) are, most likely unknowingly, confronted with the risk of criminalization and potential harm. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances (‘legal highs’) in New Zealand 下载免费PDF全文
Introduction . New Zealand's Psychoactive Substances Act (2013) established the world's first regulated market for ‘low risk’ psychoactive products (‘legal highs’). Under an interim PSA regime, 47 existing products were permitted to be continued to be sold. Aim. To explore issues with the implementation of regulatory systems to monitor the safety of products on the legal market under the interim Psychoactive Substances Act regime. Methods. Semi‐structured interviews with 30 key stakeholders, including industry, government agency, health and drug service professionals were conducted, transcribed and analysed thematically. Results. In retrospect stakeholders questioned the decision to approve strong synthetic cannabinoid smoking products, noting their health risks because of product formulation, inconsistent manufacturing practices and smoking as the means of administration. Industry actors claimed the decision to approve synthetic cannabinoid smokeable products prevented potentially safer products from gaining market share. The system for withdrawing approved products which were subsequently found to be harmful was criticised for the poor quality of data available, limited engagement with health professionals and the slowness of product withdrawal. Many of the problems with the regime were attributed to the urgency under which the legal market under the interim Psychoactive Substances Act was established and implemented. Conclusions. The selection of ‘safer’ products, implementation of the product monitoring system, and engagement with health professionals may have benefited from more time and resources. An incremental approach to establishing the new market may have made the regulatory management of the new regime more workable. [Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances (‘legal highs’) in New Zealand. Drug Alcohol Rev 2017;00:000‐000] 相似文献
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Synthesis of N‐(2‐diethylamino‐ethyl)‐4‐(4‐fluoro‐benzamido)‐2‐methoxybenzamide (desiodo‐MIP‐1145) by coupling technique and its radioiodination: a potential melanoma imaging agent 下载免费PDF全文
H. Aglan S. A. Kandil A. F. EL‐Kafrawy U. Seddik 《Journal of labelled compounds & radiopharmaceuticals》2016,59(9):372-374
Radioiodinated MIP‐1145, which specifically targets melanin, is an ideal candidate for targeted therapy of melanoma. An analogue of MIP‐1145 lacking the iodo‐substituent (desiodo‐MIP‐1145) was synthesized as a labeling precursor in three simple steps. The radioiodination of desiodo‐MIP‐1145 by iodine‐125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76%, was obtained with radiochemical purity greater than 99%. The log P value for [125I]MIP‐1145 was measured as 4.5. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2017,60(1):49-54
Tetrazoles are a common heterocyclic functionality in many biologically active molecules. [1‐14C]2‐(1H‐Tetrazol‐5‐yl)acetic acid was required as an intermediate in the synthesis of a development candidate as part of a discovery phase program to complete metabolic profiling studies. [1‐14C]2‐(1H‐Tetrazol‐5‐yl)acetic acid was prepared in 4 steps overall and in 3 radiochemical steps from K14CN in an overall 32% radiochemical yield. 相似文献
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S. De Bruyne T. L. Boos L. wyffels J. L. Goeman K. C. Rice F. De Vos 《Journal of labelled compounds & radiopharmaceuticals》2009,52(8):304-311
Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease diagnosis, staging and follow‐up providing information on the integrity of the dopaminergic neurotransmitter system in vivo. 4‐(2‐(Bis(4‐fluorophenyl)methoxy)ethyl)‐1‐(4‐iodobenzyl)piperidine (7) has nanomolar affinity for DAT and better selectivity over the other monoamine transporters compared with the existing SPECT radioligands for DAT. The aim of this study was to synthesize and evaluate [123I]‐7 as an in vivo tracer for DAT. The tributylstannyl precursor was synthesized with an overall yield of 25%. [123I]‐7 was synthesized by electrophilic destannylation with a yield of 40±10%. Radiochemical purity appeared to be >98%, whereas specific activity was at least 667 GBq/µmol. Biodistribution studies in mice showed brain uptake of 0.96±0.53%ID/g at 30 s post injection (p.i.) and 0.26±0.02%ID/g at 3 h p.i. High blood activity was observed at all time points. Pretreatment with Cyclosporin A raised brain uptake indicating that [123I]‐7 is transported by P‐glycoprotein (P‐gp) pumps. In rats, regional brain distribution of [123I]‐7 was not in agreement with DAT distribution. These results indicate that [123I]‐7 is not suitable for mapping DAT in vivo but could be a useful tracer for the P‐gp transporter. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
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Suppression of Toll‐Like Receptor 4 Dimerization by 1‐[5‐Methoxy‐2‐(2‐nitrovinyl)phenyl]pyrrolidine 下载免费PDF全文
Sang‐Il Ahn Ji‐Soo Kim Gyo‐Jeong Gu Hyeon‐Myeong Shin Ah‐Yeon Kim Hyun‐Jin Shim Yeon Joo Kim Kwang Oh Koh Joo Yang Mang Dae Young Kim Hyung‐Sun Youn 《Archiv der Pharmazie》2016,349(10):785-790
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《Journal of labelled compounds & radiopharmaceuticals》2006,49(14):1247-1258
The recently described selective and potent GlyT2 antagonist, 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide (IC50=16 nM) provided an important additional tool to further characterize GlyT2 pharmacology. In order to identify an effective PET radioligand for in vivo assessment of the GlyT‐2 transporter, 3‐(3‐[18F]fluoropropoxy)‐4‐(benzyloxy)‐N‐((1‐dimethylaminocyclopentyl) methyl)‐5‐methoxybenzamide ([18F] 3 ), a novel analog of 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide was synthesized using a one‐pot, two‐step method. The NCA radiofluorination of 1,3‐propanediol di‐p‐tosylate in the presence of K2CO3 and Kryptofix‐222 in acetonitrile gave 81% 3‐[18F]fluoropropyl tosylate, which was subsequently coupled with 4‐benzyloxy‐3‐hydroxy‐5‐methoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide in the same reaction vessel. Solvent extraction and HPLC (Eclipse XDB‐C8 column, 80/20/0.1 MeOH/H2O/Et3N, 3.0 ml/min) gave [18F] 3 in 98.5% radiochemical purity. The radiochemical yield was determined to be 14.0–16.2% at EOS, and the specific activity was 1462±342 GBq/µmol. The time of synthesis and purification was 128 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2004,47(3):181-190
2‐(4‐Methylaminostyryl)‐6‐(2‐[18F]fluoroethoxy)benzoxazole ([18F]BF‐168) was prepared and found to be a potential probe for imaging amyloid‐β. The precursor, a 6‐(2‐tosyloxyethoxy)benzoxazole derivative, was fluorinated with [18F]KF and Kryptofix 222 in acetonitrile, and the crude product purified by semi‐preparative HPLC to give [18F]BF‐168. The radiochemical purity was >95% and the maximum specific activity was 106 TBq/mmol at the end of synthesis. The synthesis time was 110 min from the end of bombardment. 2‐(4‐[N‐methyl‐11C]methylaminostyryl)‐5‐fluorobenzoxazole ([11C]BF‐145) was also prepared from 2‐(4‐aminostyryl)‐5‐fluorobenzoxazole, [11C]MeI and 5 N NaOH in DMSO, and purified by semi‐preparative HPLC. The radiochemical purity was >95% and the specific activity was 40–70 TBq/mmol at the end of synthesis. The synthesis time was 45 min from the end of bombardment. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
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Synthesis of stable isotopically labelled 3‐methylfuran‐2(5H)‐one and the corresponding strigolactones 下载免费PDF全文
Yun Cheng Wen‐hui Ding Qin Long Min Zhao Jun Yang Xiao‐qiang Li 《Journal of labelled compounds & radiopharmaceuticals》2015,58(9):355-360
Conventional synthetic procedures of strigolactones (SLs) involve the independent synthesis of ring ABC and ring D, followed by a coupling of the two fragments. Here we prepared three kinds of stable, isotopically labelled D‐ring analogues productively using a facile protocol. Then, a coupling of the D‐rings to ring ABC produced three isotope‐labelled SL derivatives. Moreover, (+)‐D3‐2′‐epi‐ 1A and (?)‐ent‐D3‐2′‐epi‐ 1A with high enantiomeric purity were obtained via chiral resolution. 相似文献
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Braulio Insuasty Alexander Gutiérrez Jairo Quiroga Rodrigo Abonia Manuel Nogueras Justo Cobo Laura Svetaz Marcela Raimondi Susana Zacchino 《Archiv der Pharmazie》2010,343(1):48-53
The present work describes the synthesis and antifungal evaluation of new 5‐arylidene‐(Z)‐2‐dimethylamino‐1,3‐thiazol‐4‐ones 4a – f , obtained by the reaction of aromatic aldehydes 1 and rhodanine 2 followed by treatment with DMF. All compounds were tested against a panel of yeasts, hialohyphomycetes, and dermatophytes using the microbroth dilution method. Compounds 4a and 4c showed antifungal activity, with compound 4a being the most active one. Compound 4a demonstrated to be fungicidal rather than fungistatic and selective activity against Cryptococcus neoformans and dermatophytes. MIC100, MIC80, and MIC50 of 4a were determined against a panel of clinical isolates of C. neoformans showing ranges of MICs between 2 and 16 μg/mL. 相似文献
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John M. Herbert Trevor W. Mathers 《Journal of labelled compounds & radiopharmaceuticals》2010,53(9):598-600
A concise preparation of [butene‐2H5]‐tiagabine hydrochloride starting from [2H6]‐γ‐butyrolactone is described. It was necessary to ring‐open the labeled γ‐butyrolactone precursor before the addition of 2‐thienyllithium to avoid cyclisation of the intermediate to a 2,2‐bis(2‐thienyl)tetrahydrofuran. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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Pradeep K. Sharma Min He Leo J. Romanczyk Jr Hagen Schroeter 《Journal of labelled compounds & radiopharmaceuticals》2010,53(10):605-612
The first synthesis of doubly labeled, [2‐13C, 4‐13C]‐(2R,3S)‐catechin 15 and [2‐13C, 4‐13C]‐(2R,3R)‐epicatechin 18 starting from labeled 2‐hydroxy‐4, 6‐bis(benzyloxy)acetophenone 3 and labeled 3, 4‐bis(benzyloxy)‐benzaldehyde 7 are described. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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Jixia Yang Gongzheng Zhang Zhaoyang Wang Zhanxiong Xiao Hongliang Wen 《Journal of labelled compounds & radiopharmaceuticals》2019,62(14):920-924
Parkinson disease (PD) is a neurodegenerative disorder characterized by the accumulation of α‐synuclein into Lewy bodies. 3‐Benzylidine‐indolin‐2‐one represents a class of compounds, which are known to inhibit the accumulation of α‐synuclein. In this paper, we report the synthesis of [13C] and [15N] labelled 1‐benzyl‐(Z)‐3‐(benzylidene)indolin‐2‐one from commercially available [13C2]‐chloroacetic acid and [15N]‐aniline in five steps. The product will be used to study its metabolites in human liver microsomes by liquid chromatography‐tandem mass spectrometry. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2006,49(12):1069-1077
2‐(4‐Methoxyphenyl)‐N‐(4‐methylbenzyl)‐N‐(1‐methylpiperidin‐4‐yl)acetamide (AC90179, 4 ), a highly potent and selective competitive 5‐HT2A antagonist, was labeled by [11C]‐methylation of the corresponding desmethyl analogue 5 with [11C]methyl triflate. The precursor molecule 5 for radiolabeling was synthesized from p‐tolylmethylamine in three steps with 46% overall yield. [11C]AC90179 was synthesized in 30 min (30 ± 5% yield, EOS) with a specific activity of 4500 ± 500 Ci/mmol and >99% chemical and radiochemical purities. Positron emission tomography studies in anesthetized baboon revealed that [11C] 4 Penetrates the blood–brain barrier (BBB) with a rapid influx and efflux of the tracer in all brain regions. Due to lack of tracer retention or specific binding, [11C] 4 cannot be used as PET ligand for imaging 5‐HT2A receptors. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
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Synthesis,molecular docking,and pharmacological evaluation of N‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives as selective COX‐2 inhibitors and anti‐inflammatory agents 下载免费PDF全文