Синтез передавальної функції регулятора напруги перетворювача активного фільтра-стабілізатора

It has been established that in order to ensure effective filtration and stabilization of the voltage of DC traction substations, it is advisable to use active filters-stabilizers. The dynamic characteristics of an active filter-stabilizer have been analyzed taking into consideration its discrete properties. It has been shown that the voltage converter in an active filter-stabilizer with bilateral pulse-width modulation for small values of control signal increment is an amplitude-pulse modulator of the second kind. In order to improve the efficiency of using an active filter-stabilizer, which is part of the DC traction substation converter, the task was set to synthesize the transfer function of its converter's voltage controller. When analyzing a closed automatic control system, it was established that the transfer function of the voltage controller, which ensures the implementation of processes of finite duration in the closed automatic control system, includes a proportional part, an integral part, and a differential part. To determine the time constants for the transfer function of the PID-controller, as well as its damping coefficient, a closed automatic control system of the active filter-stabilizer voltage converter was investigated using an apparatus of Z-transformation. The result of synthesizing the transfer function of the voltage controller has established the parameters for the controller's transfer function, which ensure that the process of finite duration is executed in a closed system of automatic control over the converter's output voltage. The transition process in the system with a stepwise input effect of the processes of finite duration has been calculated, which confirmed that the transition process in the system ends after three clock intervals of discreteness. Establishing a transition process that ends over the finite number of discrete intervals, which is determined by the order of the characteristic equation, means that the process has been optimized for performanceУстановлено, что для обеспечения эффективной фильтрации и стабилизации напряжения тяговых подстанций постоянного тока целесообразно применять активные фильтры-стабилизаторы. Выполнен анализ динамических характеристик активного фильтра-стабилизатора с учетом его дискретных свойств. Показано, что преобразователь напряжения активного фильтра-стабилизатора с двусторонней широтно-импульсной модуляцией для малых значений прироста сигнала управления представляет собой амплитудно-импульсный модулятор второго рода. С целью повышения эффективности применения активного фильтра-стабилизатора, который входит в состав преобразовательного агрегата тяговой подстанции постоянного тока, была поставлена задача синтеза передаточной функции регулятора напряжения его преобразователя. При анализе замкнутой системы автоматического регулирования установлено, что передаточная функция регулятора напряжения, обеспечивает реализацию процессов конечной длительности в замкнутой системе автоматического регулирования, имеет пропорциональную, интегральную и дифференциальную части. Для определения постоянных времени передаточной функции ПИД-регулятора и коэффициента демпфирования проведено исследование замкнутой системы автоматического регулирования напряжения преобразователя активного фильтра-стабилизатора с помощью аппарата Z-преобразования. В результате синтеза передаточной функции регулятора напряжения получены параметры передаточной функции регулятора, которые обеспечивают получение процесса конечной длительности в замкнутой системе автоматического регулирования выходного напряжения преобразователя. Выполнен расчет переходного процесса в системе при ступенчатом входном воздействии процессов конечной длительности, который подтвердил, что переходный процесс в системе заканчивается за три тактовых интервала дискретности. Получение переходного процесса, заканчивающегося за конечное число интервалов дискретности, которое определяется порядком характеристического уравнения, означает, что процесс оптимизирован по быстродействиюВстановлено, що для забезпечення ефективної фільтрації і стабілізації напруги тягових підстанцій постійного струму доцільно застосовувати активні фільтри-стабілізатори. Виконано аналіз динамічних характеристик активного фільтра-стабілізатора з урахуванням його дискретних властивостей. Показано, що перетворювач напруги активного фільтра-стабілізатора з двобічною широтно-імпульсною модуляцією для малих значень приросту сигналу управління являє собою амплітудно-імпульсний модулятор другого роду.З метою підвищення ефективності застосування активного фільтра-стабілізатора, що входить до складу перетворювального агрегату тягової підстанції постійного струму, була поставлена задача синтезу передавальної функції регулятора напруги його перетворювача. При аналізі замкнутої системи автоматичного регулювання встановлено, що передавальна функція регулятора напруги, що забезпечує реалізацію процесів кінцевої тривалості в замкнутій системі автоматичного регулювання, має пропорційну, інтегральну та диференційну частини. Для визначення постійних часу передавальної функції ПІД-регулятора та коефіцієнта демпфування проведено дослідження замкнутої системи автоматичного регулювання напруги перетворювача активного фільтра-стабілізатора за допомогою апарату Z-перетворення. В результаті синтезу передавальної функції регулятора напруги отримані параметри передавальної функції регулятора, які забезпечують одержання процесу кінцевої тривалості у замкнутій системі автоматичного регулювання вихідної напруги перетворювача. Виконано розрахунок перехідного процесу в системі при ступінчастому вхідному впливі процесів кінцевої тривалості, який підтвердив, що перехідний процес у системі закінчується за три тактових інтервали дискретності. Отримання перехідного процесу, що закінчується за кінцеве число інтервалів дискретності, яке визначається порядком характеристичного рівняння, означає, що процес оптимізовано за швидкодіє

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Synthesis of 4-(2H-[1,2,4]-Triazol-5-ylsulfanyl)-1,2-dihydropyrazol-3-one via Ring-Switching Hydrazinolysis of 5-Ethoxymethylidenethiazolo [3,2-b][1,2,4]triazol-6-one

4-(1H-[1,2,4]-Triazol-5-ylsulfanyl)-1,2-dihydropyrazol-3-one (4) was synthesized with a yield of 55% via ring-switching hydrazinolysis of 5-ethoxymethylidenethiazolo[3,2-b][1,2,4] triazol-6-one (3) in ethanol medium. The initial 1H-[1,2,4]-triazole-3-thiol (1) was modified via a two-step reaction: S-alkylation with chloroacetic acid under Williamson reaction conditions, and further one-pot cyclization–condensation with triethylorthoformate in the acetic anhydride medium, yielding compound 3. The structures of compounds 3 and 4 were confirmed by LC-MS, NMR spectra and a single X-ray diffraction analysis (for compound 4)

Synthesis of the Transfer Function of the Voltage Controller in an Active Filter-stabilizer Converter

It has been established that in order to ensure effective filtration and stabilization of the voltage of DC traction substations, it is advisable to use active filters-stabilizers. The dynamic characteristics of an active filter-stabilizer have been analyzed taking into consideration its discrete properties. It has been shown that the voltage converter in an active filter-stabilizer with bilateral pulse-width modulation for small values of control signal increment is an amplitude-pulse modulator of the second kind. In order to improve the efficiency of using an active filter-stabilizer, which is part of the DC traction substation converter, the task was set to synthesize the transfer function of its converter's voltage controller. When analyzing a closed automatic control system, it was established that the transfer function of the voltage controller, which ensures the implementation of processes of finite duration in the closed automatic control system, includes a proportional part, an integral part, and a differential part. To determine the time constants for the transfer function of the PID-controller, as well as its damping coefficient, a closed automatic control system of the active filter-stabilizer voltage converter was investigated using an apparatus of Z-transformation. The result of synthesizing the transfer function of the voltage controller has established the parameters for the controller's transfer function, which ensure that the process of finite duration is executed in a closed system of automatic control over the converter's output voltage. The transition process in the system with a stepwise input effect of the processes of finite duration has been calculated, which confirmed that the transition process in the system ends after three clock intervals of discreteness. Establishing a transition process that ends over the finite number of discrete intervals, which is determined by the order of the characteristic equation, means that the process has been optimized for performanc

Synthesis and Biological Activity Evaluation of Novel 5-Methyl-7-phenyl-3<i>H</i>-thiazolo[4,5-<i>b</i>]pyridin-2-ones

A series of 5-methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones has been designed, synthesized, and characterized by spectral data. Target compounds were screened for their antimicrobial activity against some pathogenic bacteria and fungi, and most of them showed moderate activity, especially compound 3g, which displayed the potent inhibitory effect against Pseudomonas aeruginosa and Escherichia coli with MIC value of 0.21 μM. The active thiazolopyridine derivatives 3c, 3f, and 3g were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds 3c, 3f, and 3g also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound 3g were performed through molecular docking against MurD and DNA gyrase, with binding energies and an inhibitory constant compared to the reference drug ciprofloxacin. The tested thiazolo[4,5-b]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents

Synthesis and Biological Activity Evaluation of Novel 5-Methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones

A series of 5-methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones has been designed, synthesized, and characterized by spectral data. Target compounds were screened for their antimicrobial activity against some pathogenic bacteria and fungi, and most of them showed moderate activity, especially compound 3g, which displayed the potent inhibitory effect against Pseudomonas aeruginosa and Escherichia coli with MIC value of 0.21 &mu;M. The active thiazolopyridine derivatives 3c, 3f, and 3g were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds 3c, 3f, and 3g also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound 3g were performed through molecular docking against MurD and DNA gyrase, with binding energies and an inhibitory constant compared to the reference drug ciprofloxacin. The tested thiazolo[4,5-b]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents

Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters

2-(Cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5H)-one

Multicomponent reactions effectively contribute to modern organic and medicinal chemistry. 4-Thiazolidinone core and cyclopropyl moiety are important structural motifs for design of potential biologically active molecules. In the present paper, the convenient step-economy and cost-effective synthesis of 2-(cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5H)-one (2) is described based on the application of the MCR methodology. The proposed approach includes direct one-pot interaction of 2-thioxothiazolidin-4-one (rhodanine), 4-methoxybenzaldehyde with cyclopropylamine which was used in 10% excess compare to other reagents. The structure of synthesized compound 2 was confirmed using 1H, 13C, 2D NMR, LC-MS, IR and UV spectra. The presence of prototropic amino/imino tautomerism for synthesized compound 2 was observed based on spectral analysis data. Screening of antimicrobial activity against 12 strains of Gram-positive and Gram-negative bacteria, as well as yeasts, was performed for synthesized derivative 2

Synthesis and Anticancer Activity of 2-(Alkyl-, Alkaryl-, Aryl-, Hetaryl-)-[1,2,4]triazolo[1,5-c]quinazolines

The combinatorial library of novel potential anticancer agents, namely, 2-(аlkyl-, alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-c]quinazolines, was synthesized by the heterocyclization of the аlkyl-, alkaryl-, aryl-, hetarylcarboxylic acid (3Н-quinazoline-4-ylidene)hydrazides by oxidative heterocyclization of the 4-(arylidenehydrazino)quinazolines using bromine, and by the heterocyclization of N-(2-cyanophenyl)formimidic acid ethyl ester. The optimal method for synthesis of the s-triazolo[1,5-c]quinazolines appeared to be cyclocondensation of the corresponding carboxylic acid (3H-quinazoline-4-ylidene)hydrazides. The compounds’ structures were established by 1H, 13C NMR, LC- and EI-MS analysis. The in vitro screening of anticancer activity determined the most active compound to be 3,4,5-trimethoxy-N\u27-[quinazolin-4(3H)-ylidene]benzohydrazide (3.20) in micromolar concentrations with the GI50 level (MG_MID, GI50 is 2.29). Thus, the cancer cell lines whose growth is greatly inhibited by compound 3.20 are: non-small cell lung cancer (NCI-H522, GI50=0.34), CNS (SF-295, GI50=0.95), ovarian (OVCAR-3, GI50=0.33), prostate (PC-3, GI50=0.56), and breast cancer (MCF7, GI50=0.52), leukemia (K-562, GI50=0.41; SR, GI50=0.29), and melanoma (MDA-MB-435, GI50=0.31; SK-MEL-5, GI50=0.74; UACC-62, GI50=0.32). SAR-analysis is also discussed

2-(Cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5<i>H</i>)-one

Multicomponent reactions effectively contribute to modern organic and medicinal chemistry. 4-Thiazolidinone core and cyclopropyl moiety are important structural motifs for design of potential biologically active molecules. In the present paper, the convenient step-economy and cost-effective synthesis of 2-(cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5H)-one (2) is described based on the application of the MCR methodology. The proposed approach includes direct one-pot interaction of 2-thioxothiazolidin-4-one (rhodanine), 4-methoxybenzaldehyde with cyclopropylamine which was used in 10% excess compare to other reagents. The structure of synthesized compound 2 was confirmed using 1H, 13C, 2D NMR, LC-MS, IR and UV spectra. The presence of prototropic amino/imino tautomerism for synthesized compound 2 was observed based on spectral analysis data. Screening of antimicrobial activity against 12 strains of Gram-positive and Gram-negative bacteria, as well as yeasts, was performed for synthesized derivative 2.</b