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Journal ArticleDOI

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

TL;DR: The synthesis of the dicyclohexyl analogues of DPEA and related compounds were tested as inhibitors of [(3)H]MK-801 binding to rat brain membranes and exhibited stereospecific sensitivity to the modulator spermine.
About: This article is published in Bioorganic & Medicinal Chemistry.The article was published on 2009-05-01. It has received 34 citations till now. The article focuses on the topics: Channel blocker.
Citations
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Journal ArticleDOI
TL;DR: The cross-reactivity study was performed in five different PCP IAs using urine-free, spiked samples and urine samples obtained from two 3-MeO-PCP overdose cases, and it was found that urine samples from the two overdose cases were positive for PCP in all IAs evaluated.
Abstract: Methoxetamine (MXE) and the arylcyclohexylamines 3-methoxy-PCP (3-MeO-PCP) and 4-methoxy-PCP (4-MeO-PCP) are substituted analogs of the dissociative psychoactive substances ketamine and phencyclidine (PCP), respectively. They have emerged on the new psychoactive substances (NPS) market as legal alternatives to these classically banned dissociatives. Little data has been published regarding the cross-reactivity of these NPS in PCP immunoassays (IAs). The aim of this work was to explore the possibilities of detecting 3-MeO-PCP, 4-MeO-PCP, MXE and ketamine in commercial IAs for PCP. The cross-reactivity study was performed in five different PCP IAs using urine-free, spiked samples and urine samples obtained from two 3-MeO-PCP overdose cases. 3-MeO-PCP and 4-MeO-PCP showed cross-reactivity (ranging from 1-143%) in all PCP IAs evaluated. MXE only showed very weak cross-reactivity (ranged from 0.04 to 0.25%) and ketamine was not detected in any PCP IA evaluated. Urine samples from the two overdose cases were positive for PCP in all IAs evaluated. The commercial PCP IAs evaluated exhibited utility as rapid, preliminary screening techniques for 3-MeO-PCP and 4-MeO-PCP, but not for ketamine. The low reactivity of MXE limits its detectability in the PCP IAs evaluated.

5 citations

Journal ArticleDOI
TL;DR: It is demonstrated that 16 non-competitive NR antagonists, including 5 long-chain diamines, classical NR channel blockers and several less known compounds, differ widely in their sensitivities to cationic buffer constituents.

2 citations

Journal ArticleDOI
TL;DR: In this article, a generative deep learning model has been applied to de novo drug design as a means to expand the amount of chemical space that can be explored for potential drug-like compounds, and the authors assess the application of the generative model to the N-methyl D-aspartate receptor (NMDAR) to achieve two primary objectives: (i) the creation and release of a comprehensive library of experimentally validated NMDAR phencyclidine (PCP) site antagonists to assist the drug discovery community and (ii) an analysis of both the advantages
Abstract: Uncompetitive antagonists of the N-methyl D-aspartate receptor (NMDAR) have demonstrated therapeutic benefit in the treatment of neurological diseases such as Parkinson's and Alzheimer's, but some also cause dissociative effects that have led to the synthesis of illicit drugs. The ability to generate NMDAR antagonists in silico is therefore desirable both for new medication development and for preempting and identifying new designer drugs. Recently, generative deep learning models have been applied to de novo drug design as a means to expand the amount of chemical space that can be explored for potential drug-like compounds. In this study, we assess the application of a generative model to the NMDAR to achieve two primary objectives: (i) the creation and release of a comprehensive library of experimentally validated NMDAR phencyclidine (PCP) site antagonists to assist the drug discovery community and (ii) an analysis of both the advantages conferred by applying such generative artificial intelligence models to drug design and the current limitations of the approach. We apply, and provide source code for, a variety of ligand- and structure-based assessment techniques used in standard drug discovery analyses to the deep learning-generated compounds. We present twelve candidate antagonists that are not available in existing chemical databases to provide an example of what this type of workflow can achieve, though synthesis and experimental validation of these compounds is still required.

1 citations

Journal ArticleDOI
TL;DR: In this article , an efficient route from halogenated amides to piperidines and pyrrolidines was disclosed, where amide activation, reduction of nitrile ions, and intramolecular nucleophilic substitution were integrated in a one-pot reaction.
Abstract: Piperidine and pyrrolidine derivatives are important nitrogen heterocyclic structures with a wide range of biological activities. However, reported methods for their construction often face problems of requiring the use of expensive metal catalysts, highly toxic reaction reagents or hazardous reaction conditions. Herein, an efficient route from halogenated amides to piperidines and pyrrolidines was disclosed. In this method, amide activation, reduction of nitrile ions, and intramolecular nucleophilic substitution were integrated in a one-pot reaction. The reaction conditions were mild and no metal catalysts were used. The synthesis of a variety of N-substituted and some C-substituted piperidines and pyrrolidines became convenient, and good yields were obtained.

1 citations

Journal ArticleDOI
TL;DR: In this paper , a sample of dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo-and chloro-zincate complex, was detected using X-ray powder diffraction (XRPD).
Abstract: The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.

1 citations

References
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.

12,583 citations

Journal ArticleDOI
TL;DR: In this article, a reagent formed by combining diethyl azodicarboxylate (DEAD) and triphenylphosphine (TPP) could be utilized in the intermolecular dehydration between an alcohol and various acidic components such as carboxylic acids, phosphoric diesters, imides, and active methylene compounds.
Abstract: The reagent formed by combining diethyl azodicarboxylate (DEAD) and triphenylphosphine (TPP) could be utilized in the intermolecular dehydration between an alcohol and various acidic components such as carboxylic acids, phosphoric diesters, imides, and active methylene compounds. By the use of DEAD and TPP, diols and hydroxy acids gave cyclic ethers and lactones, respectively. The reaction of nucleosides with DEAD and TPP afforded triphenylphosphoranylnucleosides. Alcohols reacted with 2,6-di-t-butyl-4-nitrophenol in the presence of DEAD and TPP to give aci-nitroesters which converted into the corresponding carbonyl compounds.

3,209 citations

01 Dec 2007

1,121 citations

Journal ArticleDOI
TL;DR: In this paper, the application of (S)-1,10-binaphthyl-2,20-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated.
Abstract: The application of (S)-1,10-binaphthyl-2,20-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated. The formation of diastereomeric host–guest complexes in solution between the CSA and the racemic substrates produced sufficient NMR signal splitting for the determination of enantiomeric excesses by Hor F-NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for obtaining good enantiodiscrimination, thus suggesting the importance of intermolecular hydrogen bonds in the stabilization of the complexes. The method was applied to the fast quantification of the enantiomeric purity of in-process samples of S-omeprazole. Chirality 00:000–000, 2009. VC 2009

885 citations