title: The synthesis and characterization of the 'research chemical' N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Gavin
authors.initials: G
authors.lastname: McLaughlin
authors.affiliation: Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Dublin Road, Athlone, Co. Westmeath, Ireland.
authors.forename: Noreen
authors.initials: N
authors.lastname: Morris
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin, 8, Ireland.
authors.forename: Pierce V
authors.initials: PV
authors.lastname: Kavanagh
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin, 8, Ireland.|Forensic Science Laboratory, Garda HQ, Dublin, 8, Ireland.
authors.forename: John D
authors.initials: JD
authors.lastname: Power
authors.affiliation: School of Chemistry, Trinity College Dublin, Dublin, 2, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Twamley
authors.affiliation: School of Chemistry, Trinity College Dublin, Dublin, 2, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, 2, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Talbot
authors.affiliation: The State Laboratory, Backweston Laboratory Complex, Young's Cross, Celbridge, Co. Kildare, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dowling
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
mesh_terms: D002186:Cannabinoids / Q000138:chemical synthesis / Q000737:chemistry; D002853:Chromatography, Liquid; D018360:Crystallography, X-Ray; D008401:Gas Chromatography-Mass Spectrometry; D013287:Illicit Drugs / Q000138:chemical synthesis / Q000737:chemistry*; D020407:Internet; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011619:Psychotropic Drugs / Q000138:chemical synthesis / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002186:Cannabinoids; D013287:Illicit Drugs; D011619:Psychotropic Drugs; D011720:Pyrazoles; C000594236:pyrazole-5-carboxamide; C031280:pyrazole
keywords: AB-CHMFUPPYCA isomers; new psychoactive substances; pyrazole-carboxamide derivatives; synthetic cannabinoids