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Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies

A series of N,N-disubstituted piperazines were synthesized containing the structural elements of both methylenedioxybenzylpiperazine (MDBP) and trifluoromethylphenylpiperazine (TFMPP) in a single molecule. These six potential designer drug molecules having a regioisomeric relationship were compared...

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Autores principales: DeRuiter, Jack, Van Cleave, Ashleigh, de Sousa Moura, Audinei, Abiedalla, Younis, Clark, C. Randall
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197089/
https://www.ncbi.nlm.nih.gov/pubmed/30483665
http://dx.doi.org/10.1080/20961790.2018.1445497
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author DeRuiter, Jack
Van Cleave, Ashleigh
de Sousa Moura, Audinei
Abiedalla, Younis
Clark, C. Randall
author_facet DeRuiter, Jack
Van Cleave, Ashleigh
de Sousa Moura, Audinei
Abiedalla, Younis
Clark, C. Randall
author_sort DeRuiter, Jack
collection PubMed
description A series of N,N-disubstituted piperazines were synthesized containing the structural elements of both methylenedioxybenzylpiperazine (MDBP) and trifluoromethylphenylpiperazine (TFMPP) in a single molecule. These six potential designer drug molecules having a regioisomeric relationship were compared in gas chromatography-mass spectrometry (GC–MS), gas chromatography-infrared spectroscopy and serotonin receptor affinity studies. These compounds were separated by capillary gas chromatography on an Rxi®-17Sil MS stationary phase film and the elution order appears to be determined by the position of aromatic ring substitution. The majority of electron ionization mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major electron ionization mass spectrometry (EI-MS) fragment ions observed in all six of these regioisomeric substances occur at m/z = 364, 229, 163 and 135. The relative intensity of the various fragment ions is also equivalent in each of the six EI-MS spectra. The vapour phase infrared spectra provide a number of absorption bands to differentiate among the six individual compounds on this regioisomeric set. Thus, the mass spectra place these compounds into a single group and the vapour phase infrared spectra differentiate among the six regioisomeric possibilities. All of the TFMPP–MDBP regioisomers displayed significant binding to 5-HT(2B) receptors and in contrast to 3-TFMPP, most of these TFMPP–MDBP isomers did not show significant binding at 5-HT(1) receptor subtypes. Only the 3-TFMPP-3,4-MDBP (Compound 5) isomer displayed affinity comparable to 3-TFMPP at 5-HT(1A) receptors (K(i) = 188 nmol/L).
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spelling pubmed-61970892018-11-27 Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies DeRuiter, Jack Van Cleave, Ashleigh de Sousa Moura, Audinei Abiedalla, Younis Clark, C. Randall Forensic Sci Res Original Article A series of N,N-disubstituted piperazines were synthesized containing the structural elements of both methylenedioxybenzylpiperazine (MDBP) and trifluoromethylphenylpiperazine (TFMPP) in a single molecule. These six potential designer drug molecules having a regioisomeric relationship were compared in gas chromatography-mass spectrometry (GC–MS), gas chromatography-infrared spectroscopy and serotonin receptor affinity studies. These compounds were separated by capillary gas chromatography on an Rxi®-17Sil MS stationary phase film and the elution order appears to be determined by the position of aromatic ring substitution. The majority of electron ionization mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major electron ionization mass spectrometry (EI-MS) fragment ions observed in all six of these regioisomeric substances occur at m/z = 364, 229, 163 and 135. The relative intensity of the various fragment ions is also equivalent in each of the six EI-MS spectra. The vapour phase infrared spectra provide a number of absorption bands to differentiate among the six individual compounds on this regioisomeric set. Thus, the mass spectra place these compounds into a single group and the vapour phase infrared spectra differentiate among the six regioisomeric possibilities. All of the TFMPP–MDBP regioisomers displayed significant binding to 5-HT(2B) receptors and in contrast to 3-TFMPP, most of these TFMPP–MDBP isomers did not show significant binding at 5-HT(1) receptor subtypes. Only the 3-TFMPP-3,4-MDBP (Compound 5) isomer displayed affinity comparable to 3-TFMPP at 5-HT(1A) receptors (K(i) = 188 nmol/L). Taylor & Francis 2018-04-05 /pmc/articles/PMC6197089/ /pubmed/30483665 http://dx.doi.org/10.1080/20961790.2018.1445497 Text en © 2018 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
DeRuiter, Jack
Van Cleave, Ashleigh
de Sousa Moura, Audinei
Abiedalla, Younis
Clark, C. Randall
Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
title Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
title_full Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
title_fullStr Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
title_full_unstemmed Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
title_short Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
title_sort disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197089/
https://www.ncbi.nlm.nih.gov/pubmed/30483665
http://dx.doi.org/10.1080/20961790.2018.1445497
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