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101.
Johan F. A. Pijnenborg Eline A. Visser Dr. Marek Noga Emiel Rossing Raisa Veizaj Prof. Dirk J. Lefeber Dr. Christian Büll Dr. Thomas J. Boltje 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(12):4022-4027
Fucosylation of glycans impacts a myriad of physiological and pathological processes. Inhibition of fucose expression emerges as a potential therapeutic avenue for example in cancer, inflammation, and infection. In this study, we found that protected 2-fluorofucose 1-phosphate efficiently inhibits cellular fucosylation with a four to seven times higher potency than known inhibitor 2FF, independently of the anomeric stereochemistry. Nucleotide sugar analysis revealed that both the α- and β-GDP-2FF anomers are formed inside the cell. In conclusion, we developed A2FF1P and B2FF1P as potent new tools for studying the role of fucosylation in health and disease and they are potential therapeutic candidates. 相似文献
102.
《Biomedical chromatography : BMC》2017,31(3)
MLN0128, an mTOR kinase inhibitor, is currently undergoing clinical investigation for treatment of a variety of cancers. To support this work, an LC–MS/MS method has been developed for the determination of MLN0128 in human plasma. A structural analog STK040263 was used as the internal standard. Both MLN0128 and the IS were first extracted from plasma using methyl tert ‐butyl ether; then separated on a Waters XTerra® MS C18 column using a mobile phase consisting of methanol–acetonitrile–10.0 mm ammonium formate (34:6:60, v /v/v) at a flow rate of 0.300 mL min−1. Quantitation of MLN0128 was done by positive electrospray ionization tandem mass spectrometry in multiple‐reaction‐monitoring mode. This method has a total run time of <4 min with the retention times of 1.95 and 2.94 min for the IS and MLN0128, respectively. The method has been validated per the US Food and Drug Administration guidance for bioanalytical method validation. It has a calibration range of 0.100–50.0 ng mL−1 in human plasma with a correlation coefficient > 0.999. The overall assay accuracy and precision were ≤ ± 4 and ≤8%, respectively. The IS normalized recovery of MLN0128 was 98–100%. The stability studies showed that MLN0128 was stable under all tested conditions. The method developed may be useful for clinical studies of MLN0128. 相似文献
103.
《Biomedical chromatography : BMC》2017,31(11)
A rapid and highly specific assay was developed and validated for the estimation of ZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as specificity, matrix effect, precision, accuracy, recovery, stability, etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising: (A) 0.2% ammonia in purified water; (B) 0.1% formic acid in isopropyl alcohol/methanol (1: 1 v /v); and (C) acetonitrile at a flow rate of 1 mL/min on an ACE‐5, C18 (4.6 × 50 mm) column with a run time of 5.5 min. The quantitation of ZYDPLA1 was achieved by the summation of four multiple reaction mode transitions (m/z 399.7 → 383.0, 399.7 → 276.10, 399.7 → 153.20 and 399.7 → 127.20), while that of the internal standard was by a single multiple reaction mode transition (m/z 309.10 → 281.00). The lower limit of quantitation achieved was 0.01 μg/mL and the method showed linearity from 0.01 to 25 μg/mL. The intra‐ and inter‐day precision (%CV) of the quality control samples was within 8.81% and accuracy was ±10% of nominal values. This novel method was applied for evaluation of toxicokinetics of ZYDLA1 in rats. 相似文献
104.
Jerzy Zakrzewski Maria Krawczyk 《Phosphorus, sulfur, and silicon and the related elements》2013,188(7):1880-1903
Thio and seleno analogs of fenuron, isoproturon, chlorotoluron, metoxuron, monuron, and diuron were synthesized from the corresponding aryl amines. Their reaction with thiophosgene leads to isothiocyanates. Aryl amines were also converted (via isocyanides) to isoselenocyanates. The reaction of both isothio- and isoselenocyanates with dimethylamine affords the corresponding thio and seleno analogs of the above-mentioned urea herbicides. Herbicidal activity of the synthesized compounds was slightly lower than the activity of the parent urea herbicides. The thio and seleno analogs as well as the parent ureas showed good fungicidal activity at a concentration of 200 ppm against selected fungi. 相似文献
105.
106.
An efficient three-step synthesis of COX-2 inhibitor inotilone from acetaldoxime is described. The structure of inotilone was elucidated via an aldol reaction between 5-methyl-3(2H)-furanone and 3,4-dihydroxybenzaldehyde. This approach describes a convenient pathway to 5-alkyl-3-furanones through isoxazole chemistry. 相似文献
107.
Charles F. Nutaitis 《合成通讯》2013,43(7):1081-1085
A convenient one-pot synthesis of symmetric vicinal diamines utilizing sodium borohydride/trifluoroacetic acid reduction methodology is described . 相似文献
108.
Herein we report a facile synthesis of esters of bis‐α‐aminoalkylphosphinic acids obtained by an addition of Cbz‐protected phosphinic analogues of amino acid methyl esters to an appropriate imine in refluxing benzene. Complete deprotection of the esters could be achieved in one step by the action of 30% HBr in acetic acid. 相似文献
109.
采用体外酶抑制活性检测方法结合超滤质谱(UF-LC/MS)筛选方法对中药提取物中的α-葡萄糖苷酶抑制剂进行了筛选.以4-硝基苯-α-D-吡喃葡萄糖苷(PNPG)为底物,阿卡波糖为阳性对照药,对5种富含黄酮类化合物的中药提取物进行了α-葡萄糖苷酶抑制活性的初步测定.结果表明,银杏叶具有最强的α-葡萄糖苷酶抑制活性,可作为进一步复筛的对象.利用超滤质谱技术对银杏叶中潜在的α-葡萄糖苷酶抑制剂进行了筛选,从中筛选出4种潜在的α-葡萄糖苷酶抑制剂,并利用液相色谱-串联质谱技术(LC-MSn)对其结构进行了鉴定.本文结果为开发新一代安全有效的降糖药物奠定了基础. 相似文献
110.
Dimitra A. Lambropoulou Ioannis K. Konstantinou Triantafyllos A. Albanis 《International journal of environmental analytical chemistry》2013,93(3-4):223-240
Abstract This study develops a method for solid phase microextraction (SPME) of ten widespread herbicides from water. The selected herbicides belong to different chemical groups are EPTC, molinate, propachlor, trifluralin, atrazine, propazine, terbuthylazine, prometryne, alachlor. Their determination was carried out by gas chromatography with flame thermionic and mass spectrometric detection. To perform the SPME, two types of fibre have been assayed: Carbowax-divinylbenzene (CW-DVB) of 65 μm thickness and polydimethylsiloxane-divinylbenzene (PDMS-DVB) of 65 μm thickness. The main factors affecting the SPME process such as pH, ionic strength, methanol content, memory effect, stirring rate and adsorption-time profile were studied. The method was applied to spiked natural waters such as ground water, sea water, lake water and river water in a concentration range of 0.1 to 10 μg/L. Limits of detection with each of the detectors were determined to be 1 – 20 ng/L in PDMS-DVB and 2–20 ng/L CW-DVB fibres. The recoveries of herbicides compared to distilled water were in relatively high levels 78.3–127.3 % and the average r2 values of the calibration curves were above 0.99 for all the analytes. The SPME conditions were finally optimized in order to obtain maximum sensitivity and samples were applied for the trace-level determination in river water samples originating from Ioannina region (Greece). 相似文献