NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds

Berger, Michael L.; Schweifer, Anna; Rebernik, Patrick; Hammerschmidt, Friedrich

doi:10.1016/j.bmc.2009.03.025

Cited by 38 publications

(24 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two "additional" 13 C chemical shifts were reported with the hydrochloride salt. [14] When acquiring the NMR spectra for the HCl salt of diphenidine, a similar observation was made and 2-D HMQC analysis carried out here suggested that C α and C β carbons appeared as four 13 C chemical shifts as opposed to two. The free base, however, did not reveal distinct signals.…”

Section: Mass Spectrometry and Chromatographysupporting

confidence: 71%

“…As the salt was semi-soluble in acetone, the crystals were washed three times with a 50:50 mixture of EtOAc and diethyl ether (Et 2 O). The crystals were dried and crystallized at [21] 158 °C, [22] 207−208.5 °C, [22] 207−209 °C, [22] 207−209 °C (HCl × H 2 O, [14] 207 °C [20] ). 1 …”

Section: Synthesis Proceduresmentioning

confidence: 99%

“…This procedure was also employed by Berger et al for the preparation of diphenidine and its single enantiomers [14] and it previously provided convenient access to the preparation of PCP and PCPy analogues. [19] The synthesis of diphenidine was reported first in 1924 and was based on a modified Bruylanys reaction between benzylmagnesium bromide and the corresponding α-arylamino nitrile.…”

Section: Electrophysiologymentioning

confidence: 99%

“…The implementation of ESI-MS/MS did not reveal differential fragmentations between isomers (1)/(2) and (3)/(4) as observed under EI and CI conditions (Figure 3). However, a difference in relative abundance observed 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The 1 H and 13 C spectra of (1), (R)- (1) and (S)- (1) free base and the hydrochloride salt have been previously published [14,31] and the results obtained in the present study were largely consistent. Two "additional" 13 C chemical shifts were reported with the hydrochloride salt.…”

Section: Mass Spectrometry and Chromatographymentioning

confidence: 99%

See 3 more Smart Citations

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

Wallach

Kavanagh

McLaughlin

et al. 2014

Drug Testing and Analysis

View full text Add to dashboard Cite

Substances with the diphenylethylamine nucleus represent a recent addition to the product catalog of dissociative agents sold as ‘research chemicals’ on the Internet. Diphenidine, i.e. 1‐(1,2‐diphenylethyl)piperidine (1,2‐DEP), is such an example but detailed analytical data are less abundant. The present study describes the synthesis of diphenidine and its most obvious isomer, 1‐(2,2‐diphenylethyl)piperidine (2,2‐DEP), in order to assess the ability to differentiate between them. Preparation and characterization were also extended to the two corresponding pyrrolidine analogues 1‐(1,2‐diphenylethyl)‐ and 1‐(2,2‐diphenylethyl)pyrrolidine, respectively. Analytical characterizations included high‐resolution electrospray mass spectrometry (HR‐ESI‐MS), liquid chromatography ESI‐MS/MS, gas chromatography ion trap electron and chemical ionization MS, nuclear magnetic resonance spectroscopy (NMR) and infrared spectroscopy. Differentiation between the two isomeric pairs was possible under GC‐(EI/CI)‐MS conditions and included the formation of distinct iminium ions, such as m/z 174 for 1,2‐DEP and m/z 98 for 2,2‐DEP, respectively. The pyrrolidine counterparts demonstrated similar phenomena including the expected mass difference of 14 Da due to the lack of one methylene unit in the ring. Two samples obtained from an Internet vendor provided confirmation that diphenidine was present in both samples, concurring with the product label. Finally, it was confirmed that diphenidine (30 μM) reduced N‐methyl‐D‐aspartate‐mediated field excitatory postsynaptic potentials (NMDA‐fEPSPs) to a similar extent to that of ketamine (30 μM) when using rat hippocampal slices. The appearance of 1,2‐ diphenylethylamines appears to reflect the exploration of alternatives to arylcyclohexylamine‐type substances, such as methoxetamine, PCP and PCPy‐based analogues that also show NMDA receptor activity as demonstrated here for diphenidine. Copyright © 2014 John Wiley & Sons, Ltd.

show abstract

Section: Mass Spectrometry and Chromatographysupporting

confidence: 71%

Section: Synthesis Proceduresmentioning

confidence: 99%

Section: Electrophysiologymentioning

confidence: 99%

Section: Mass Spectrometry and Chromatographymentioning

confidence: 99%

See 2 more Smart Citations

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

Wallach

Kavanagh

McLaughlin

et al. 2014

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…The first synthesis of diphenidine was published in 1924 by Christiaen who used a modified Brulyants reaction, similar to the reaction later used by Maddox in the first PCP synthesis. [191][192][193] Importantly diphenidine has been shown to act as an NMDAR antagonist [193] and can be viewed as an MK-801 homeomorph and shares structural features with arylcyclohexylamines. [191][192][193] Importantly diphenidine has been shown to act as an NMDAR antagonist [193] and can be viewed as an MK-801 homeomorph and shares structural features with arylcyclohexylamines.…”

Section: The Diarylethylaminesmentioning

confidence: 99%

From PCP to MXE: a comprehensive review of the non‐medical use of dissociative drugs

Morris

Wallach

2014

Drug Testing and Analysis

209

243

View full text Add to dashboard Cite

PCP or phencyclidine was discovered in 1956 and soon became a popular street drug. Dissociatives including PCP, ketamine, and dextromethorphan have been used non-medically for their mind-altering effects for over 60 years. Many of these compounds have also been used clinically and in legitimate research. At least 14 derivatives of PCP were sold for non-medical and illict use from the late 1960s until the 1990s. With the advent of the Internet, the drug market underwent a dramatic evolution. While initially gray-market chemical vendors offering dextromethorphan and ketamine thrived, most recently the market has shifted to legal high and online-based research chemical vendors. Starting with the first dissociative research chemical, 4-MeO-PCP in 2008, the dissociative research chemical market has rapidly evolved and currently comprises at least 12 dissociatives, almost half of which were unknown in the scientific literature prior to their introduction. Several of these, including methoxetamine, have reached widespread use internationally. A historical account of non-medical use of over 30 dissociative compounds was compiled from a diverse collection of sources. The first complete portrait of this underground market is presented along with the relevant legal, technological, and scientific developments which have driven its evolution.

show abstract

Pd(II)‐Catalyzed, γ‐C(sp²)−H Alkoxylation in α‐Methylbenzylamine, Phenylglycinol, 3‐Amino‐3‐Phenylpropanol Toward Enantiopure Aryl Alkyl Ethers

et al. 2022

View full text Add to dashboard Cite

This paper reports the synthesis of enantiopure aryl alkyl ethers via the Pd(II)-catalyzed picolinamide-aided γ-C(sp 2 )À H alkoxylation of various enantiopure α-alkylbenzylamine derivatives using alcohols. Enantiopure α-methylbenzylamines and amino alcohol substrates such as 2amino-2-phenylethanol (phenylglycinol) and 3-amino-3-phenylpropanol were subjected to the γ-C(sp 2 )À H alkoxylation (etherification) with alcohols using PIDA. α-Alkylbenzylamines and phenylglycinols are valuable building blocks in organic synthesis and medicinal chemistry research areas. Accordingly, this work has enabled the assembling of various enantiopure ortho-alkoxylated α-methylbenzylamine and 2-amino-2-phenylethanol (phenylglycinol) and 3-amino-3-phenylpropanol derivatives containing aryl alkyl ether functionality. We have shown the utility of ortho-alkoxylated αmethylbenzylamine derivatives for assembling enantiopure α-methylbenzylamine-based sulfamoylcarbamates and carboxamides which are structurally related to the bio-active compounds known in the literature. This work demonstrates the substrate scope elaboration in CÀ H functionalization and etherification through the CÀ O bond-forming process and synthesis of aryl alkyl ether functionality containing enantiopure α-alkylbenzylamines.

show abstract

NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds

Cited by 38 publications

References 40 publications

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

From PCP to MXE: a comprehensive review of the non‐medical use of dissociative drugs

Pd(II)‐Catalyzed, γ‐C(sp²)−H Alkoxylation in α‐Methylbenzylamine, Phenylglycinol, 3‐Amino‐3‐Phenylpropanol Toward Enantiopure Aryl Alkyl Ethers

Contact Info

Product

Resources

About

NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds

Cited by 38 publications

References 40 publications

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

From PCP to MXE: a comprehensive review of the non‐medical use of dissociative drugs

Pd(II)‐Catalyzed, γ‐C(sp2)−H Alkoxylation in α‐Methylbenzylamine, Phenylglycinol, 3‐Amino‐3‐Phenylpropanol Toward Enantiopure Aryl Alkyl Ethers

Contact Info

Product

Resources

About

Pd(II)‐Catalyzed, γ‐C(sp²)−H Alkoxylation in α‐Methylbenzylamine, Phenylglycinol, 3‐Amino‐3‐Phenylpropanol Toward Enantiopure Aryl Alkyl Ethers