McLaughlin Gavin, Morris Noreen, Kavanagh Pierce V, Power John D, Twamley Brendan, O'Brien John, Talbot Brian, Dowling Geraldine, Brandt Simon D
Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Dublin Road, Athlone, Co. Westmeath, Ireland.
Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin, 8, Ireland.
Drug Test Anal. 2016 Sep;8(9):920-9. doi: 10.1002/dta.1864. Epub 2015 Sep 11.
This study presents the identification of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide that was termed 3,5-AB-CHMFUPPYCA. This compound was obtained from a UK-based Internet vendor, who erroneously advertised this 'research chemical' as AZ-037 and which would have been associated with (S)-N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide. The presence of the pyrazole core indicates a bioisosteric replacement of an indazole ring that is frequently associated with synthetic cannabinoids of the PINACA, FUBINACA, and CHMINACA series. The pyrazole ring system present in 3,5-AB-CHMFUPPYCA gives rise to the regioisomer N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide (named 5,3-AB-CHMFUPPYCA) and both isomers were synthesized using two specific routes which supported the correct identification of the 'research chemical' as 3,5-AB-CHMFUPPYCA. Both isomers could be conveniently differentiated. Interestingly, a route specific chlorine-containing by-product also was observed during the synthesis of 3,5-AB-CHMFUPPYCA and identified as N-(1-amino-3-methyl-1-oxobutan-2-yl)-4-chloro-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide. An extensive analytical characterization included chromatographic, spectroscopic, mass spectrometric platforms as well as crystal structure analysis. The syntheses and analytical characterizations of both AB-CHMFUPPYCA isomers are reported for the first time and serves as a reminder that the possibility of mislabeling of 'research chemicals' cannot be excluded. The pharmacological activities of both AB-CHMFUPPYCA isomers remain to be explored. Copyright © 2015 John Wiley & Sons, Ltd.
本研究介绍了对N-(1-氨基-3-甲基-1-氧代丁烷-2-基)-1-(环己基甲基)-3-(4-氟苯基)-1H-吡唑-5-甲酰胺（称为3,5-AB-CHMFUPPYCA）的鉴定。该化合物购自一家英国互联网供应商，该供应商错误地将这种“研究化学品”宣传为AZ-037，而它原本与(S)-N-(1-氨基-3-甲基-1-氧代丁烷-2-基)-1-(5-氟戊基)-5-(4-氟苯基)-1H-吡唑-3-甲酰胺有关。吡唑核心的存在表明吲唑环发生了生物电子等排体取代，吲唑环常与PINACA、FUBINACA和CHMINACA系列的合成大麻素相关。3,5-AB-CHMFUPPYCA中存在的吡唑环系统产生了区域异构体N-(1-氨基-3-甲基-1-氧代丁烷-2-基)-1-(环己基甲基)-5-(4-氟苯基)-1H-吡唑-3-甲酰胺（命名为5,3-AB-CHMFUPPYCA），并且使用两条特定路线合成了这两种异构体，这支持了将该“研究化学品”正确鉴定为3,5-AB-CHMFUPPYCA。两种异构体可以方便地加以区分。有趣的是，在3,5-AB-CHMFUPPYCA的合成过程中还观察到了一种特定路线的含氯副产物，并将其鉴定为N-(1-氨基-3-甲基-1-氧代丁烷-2-基)-4-氯-1-(环己基甲基)-3-(4-氟苯基)-1H-吡唑-5-甲酰胺。广泛的分析表征包括色谱、光谱、质谱平台以及晶体结构分析。首次报道了两种AB-CHMFUPPYCA异构体的合成和分析表征，这提醒人们不能排除“研究化学品”标签错误的可能性。两种AB-CHMFUPPYCA异构体的药理活性仍有待探索。版权所有© 2015约翰·威利父子有限公司。
