Low-Complexity Tracking Control of Unknown Strict-Feedback Systems With Quantitative Performance Guarantees.

This article is concerned with the prescribed performance tracking control problem for the strict-feedback systems with unknown nonlinearities and unmatched disturbances. The challenge lies in the realization of a complete performance specification for trajectory tracking in the sense of quantitatively regulating the peak value, overshoot, settling time, and accuracy while ensuring that the initial condition holds naturally. To this end, an error transformation, equipped with a shifting function, is introduced and incorporated with a new-type barrier function. Then, a class of performance functions is exploited to quantify the settling times and steady-state bounds of the intermediate errors. Moreover, to improve the flexibility of formulating performance specifications for the tracking error, a pair of asymmetric performance boundaries are further designed. With their combination, a novel robust prescribed performance control (PPC) approach is proposed in this article. It not only achieves the quantitative performance guarantees but also preserves the unique simplicity of PPC, evading the needs for function approximation, parameter identification, disturbance estimation, derivative calculation, or command filtering. The above theoretical findings are confirmed via three simulation studies.

Detection of Leishmania infantum Antibodies in Stray Dogs from Nonendemic Areas in Bulgaria.

Background: Leishmaniasis is a zoonotic protozoan infection which is endemic in parts of Europe. Dogs are commonly affected by Leishmania infantum and are regarded as the main reservoir for humans' infection. Sporadic human cases are reported annually, mainly from the endemic south part of Bulgaria. However, no recent data on canine leishmaniasis geographical distribution in Bulgaria have been published. The aim of this study was to investigate the current seroprevalence rate of L. infantum in stray dogs from areas where this infection was not previously reported. Results: The estimated overall seroprevalence rate was 8.3% (95% confidence interval [CI]: 2.6-14.0) with no significant difference between the two examined districts [χ2 (1, N = 90) = 0.32, p = 0.69]. In Sofia, the seropositivity was 7.2% (95% CI: 0.9-13.5) and in Sofia (stolitsa) 11.0% (95% CI: 0-23.0). No association between sex and serological status [χ2 (1, N = 90) = 1.83, p = 0.27] and age and seropositivity [χ2 (2, N = 90) = 1.98, p = 0.52] was detected. High levels of antibodies (fourfold increase from the assay's cut-off) were observed in half of the positive dogs.

Adaptive fuzzy prescribed time tracking control for nonlinear systems with input saturation.

This article investigates the adaptive fuzzy prescribed time tracking control problem for a class of strict-feedback systems simultaneously considering the user-defined asymmetric tracking performance, input saturation, and external disturbances. From the perspective of ensuring the reliability for control implementation, a saturation-based fixed-time funnel boundary is constructed by embedding the modification signals related to input saturation errors into a funnel function, which is capable of automatically enlarging or recovering itself when input saturation occurs or disappears, thereby reducing the risk of system singularity. Subsequently, by constructing a fixed-time tracking performance function, any known bounded tracking error is recast into a new variable with a zero initial value. With such a treatment, funnel boundaries are no longer redeveloped for different initial tracking errors, and meanwhile the behavior of the tracking error is pre-specified as needed over a finite time interval. Also, auxiliary systems are devised to generate the aforesaid modification signals, while compensating for the adverse impact resulting from input saturation. Remarkably, by feat of the backstepping design based on the fuzzy approximation, it is proven that the tracking error converges to a user-defined region within a prescribed time (known as the practically prescribed time tracking), which is achieved without the fractional power feedback of system states. Finally, two simulation examples are presented to confirm the feasibility and effectiveness of the developed approach.

Micellar Form of a Ferrocene-Containing Camphor Sulfonamide with Improved Aqueous Solubility and Tumor Curing Potential.

The discovery of new anticancer drugs with а higher, more specific activity and diminished side effects than the conventional chemotherapeutic agents is a tremendous challenge to contemporary medical research and development. To achieve a pronounced efficacy, the design of antitumor agents can combine various biologically active subunits in one molecule, which can affect different regulatory pathways in cancer cells. We recently demonstrated that a newly synthesized organometallic compound, a ferrocene-containing camphor sulfonamide (DK164), possesses promising antiproliferative activity against breast and lung cancer cells. However, it still encounters the problem of solubility in biological fluids. In this work, we describe a novel micellar form of DK164 with significantly improved solubility in aqueous medium. DK164 was embedded in biodegradable micelles based on a poly(ethylene oxide)-b-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone)-b-poly(ethylene oxide) triblock copolymer (PEO113-b-P(CyCL3-co-CL46)-b-PEO113), and the physicochemical parameters (size, size distribution, zeta potential, encapsulation efficiency) and biological activity of the obtained system were studied. We used cytotoxicity assays and flow cytometry to determine the type of cell death, as well as immunocytochemistry to assess the influence of the encapsulated drug on the dynamics of cellular key proteins (p53 and NFkB) and the process of autophagy. According to our results, the micellar form of the organometallic ferrocene derivate (DK164-NP) exhibited several advantages compared to the free substance, such as higher metabolic stability, better cellular uptake, improved bioavailability, and long-term activity, maintaining nearly the same biological activity and anticancer properties of the drug.

Structure and Conformational Mobility of OLED-Relevant 1,3,5-Triazine Derivatives.

A series of OLED-relevant compounds, consisting of 1,3,5-triazine core linked to various aromatic arms by amino group, has been synthesized and characterized. The studied compounds exist in solution as a mixture of two conformers, a symmetric propeller and asymmetric conformer, in which one of the aromatic arms is rotated around the C-N bond. At temperatures below -40 °C, the VT NMR spectra in DMF-d7 are in a slow exchange regime, and the signals of two conformers can be elucidated. At temperatures above 100 °C, the VT NMR spectra in DMSO-d6 are in a fast exchange regime, and the averaged spectra can be measured. The ratio of symmetric and asymmetric conformers in DMF-d7 varies from 14:86 to 50:50 depending on the substituents. The rotational barriers of symmetric and asymmetric conformers in DMF-d7 were measured for all compounds and are in the interval from 11.7 to 14.7 kcal/mol. The ground-state energy landscapes of the studied compounds, obtained by DFT calculations, show good agreement with the experimental rotational barriers. The DFT calculations reveal that the observed chemical exchange occurs by the rotation around the C(1,3,5-triazine)-N bond. Although some of the compounds are potentially tautomeric, the measured absorption and emission spectra do not indicate proton transfer neither in the ground nor in the excited state.

Molecular Insight into Mycobacterium tuberculosis Resistance to Nitrofuranyl Amides Gained through Metagenomics-like Analysis of Spontaneous Mutants.

We performed synthesis of new nitrofuranyl amides and investigated their anti-TB activity and primary genetic response of mycobacteria through whole-genome sequencing (WGS) of spontaneous resistant mutants. The in vitro activity was assessed on reference strain Mycobacterium tuberculosis H37Rv. The most active compound 11 was used for in vitro selection of spontaneous resistant mutants. The same mutations in six genes were detected in bacterial cultures grown under increased concentrations of 11 (2×, 4×, 8× MIC). The mutant positions were presented as mixed wild type and mutant alleles while increasing the concentration of the compound led to the semi-proportional and significant increase in mutant alleles. The identified genes belong to different categories and pathways. Some of them were previously reported as mediating drug resistance or drug tolerance, and counteracting oxidative and nitrosative stress, in particular: Rv0224c, fbiC, iniA, and Rv1592c. Gene-set interaction analysis revealed a certain weak interaction for gene pairs Rv1592-Rv1639c and Rv1592-Rv0224c. To conclude, this study experimentally demonstrated a multifaceted primary genetic response of M. tuberculosis to the action of nitrofurans. All three 11-treated subcultures independently presented the same six SNPs, which suggests their non-random occurrence and likely causative relationship between compound action and possible resistance mechanism.

Base-promoted direct amidation of esters: beyond the current scope and practical applications.

The base-promoted direct amidation of unactivated esters is among the most useful reactions for amide bond formation in contemporary organic chemistry. The intensive research in this area has led to the development of a number of new methods to achive this transformation. However, to date, the existing literature is more methodological and in many instances lacks practical directions. Therefore, the full potential of this transformation is yet to be revealed by broadening the substrate scope. In a search for new practical applications of the amidation reaction, herein we present a comprehensive study of a number of base-promoted direct amidations that encompass a wide range of amines and esters. Furthermore, we applied our findings in the synthesis of phosphoramidates and several industrially relevant products.

In Vitro Anticancer Activity of Two Ferrocene-Containing Camphor Sulfonamides as Promising Agents against Lung Cancer Cells.

The successful design of antitumour drugs often combines in one molecule different biologically active subunits that can affect various regulatory pathways in the cell and thus achieve higher efficacy. Two ferrocene derivatives, DK-164 and CC-78, with different residues were tested for cytotoxic potential on non-small lung cancer cell lines, A549 and H1299, and non-cancerous MRC5. DK-164 demonstrated remarkable selectivity toward cancer cells and more pronounced cytotoxicity against A549. The cytotoxicity of CC-78 toward H1299 was even higher than that of the well-established anticancer drugs cisplatin and tamoxifen, but it did not reveal any noticeable selective effect. DK-164 showed predominantly pro-apoptotic activity in non-small cell lung carcinoma (NSCLC) cells, while CC-78 caused accidental cell death with features characteristic of necrosis. The level of induced autophagy was similar for both substances in cancer cells. DK-164 treatment of A549, H1299, and MRC5 cells for 48 h significantly increased the fluorescence signal of the NFkB (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells) protein in the nucleus in all three cell lines, while CC-78 did not provoke NFkB translocation in any of the tested cell lines. Both compounds caused a significant transfer of the p53 protein in the nucleus of A549 cells but not in non-cancerous MRC5 cells. In A549, DK-164 generated oxidative stress close to the positive control after 48 h, while CC-78 had a moderate effect on the cellular redox status. In the non-cancerous cells, MRC5, both compounds produced ROS similar to the positive control for the same incubation period. The different results related to the cytotoxic potential of DK-164 and CC-78 associated with the examined cellular mechanisms induced in lung cancer cells might be used to conclude the specific functions of the various functional groups in the ferrocene compounds, which can offer new perspectives for the design of antitumour drugs.

Chiral Aminoalcohols and Squaric Acid Amides as Ligands for Asymmetric Borane Reduction of Ketones: Insight to In Situ Formed Catalytic System by DOSY and Multinuclear NMR Experiments.

A series of squaric acid amides (synthesized in 66-99% isolated yields) and a set of chiral aminoalcohols were comparatively studied as ligands in a model reaction of reduction of α-chloroacetophenone with BH3•SMe2. In all cases, the aminoalcohols demonstrated better efficiency (up to 94% ee), while only poor asymmetric induction was achieved with the corresponding squaramides. A mechanistic insight on the in situ formation and stability at room temperature of intermediates generated from ligands and borane as possible precursors of the oxazaborolidine-based catalytic system has been obtained by 1H DOSY and multinuclear 1D and 2D (1H, 10/11B, 13C, 15N) NMR spectroscopy of equimolar mixtures of borane and selected ligands. These results contribute to better understanding the complexity of the processes occurring in the reaction mixture prior to the possible oxazaborolidine formation, which play a crucial role on the degree of enantioselectivity achieved in the borane reduction of α-chloroacetophenone.

Azo-hydrazone molecular switches: Synthesis and NMR conformational investigation.

A series of five intramolecularly hydrogen-bonded arylhydrazone (aryl = phenol, p-nitrophenol, anisole, quinoline) derived molecular switches have been synthesized and characterized by NMR and HRMS techniques. It was found that the compounds exist as different isomers in solution. An investigation of both conformational and/or configurational changes of the azo-hydrazone compounds was carried out by 1D 1 H- and 13 C- spectra, 2D NOESY, COSY, HSQC, and HMBC techniques. It was found that these stimuli-responsive molecular switches exist mainly in the E form by intramolecularly hydrogen bonded between NH and the pyridine nitrogen at equilibrium. Deprotonation of the neutral E form yields the E' deprotonated isomer. Prediction of 13 C-NMR chemical shifts was achieved by DFT quantum mechanical calculations. Anions have traditionally been difficult to calculate correctly, so calculations of the anion using different functionals, basis sets, and solvent effects are also included. Deuterium isotope effects on the 13 C-NMR chemical shifts were employed in the assignments and furthermore utilized as indicators of intramolecular hydrogen bonding. Studies in various organic solvents including CDCl3 , CD3 CN, and DMSO-d6 were also performed aiming to monitor dynamic changes over several days. The effect of the hydrogen bonded solvents leads to Z forms.

[Rheumatic pain and chronic pain in children, adolescents and young adults]. / Rheumaschmerz und chronischer Schmerz bei Kindern, Jugendlichen und jungen Erwachsenen.

BACKGROUND: Rheumatic diseases, such as juvenile idiopathic arthritis (JIA), are typically associated with acute pain mainly caused by inflammation. Chronic pain is described as pain lasting at least 3 months. In JIA patients chronic pain may occur despite successful treatment. Chronic pain and pain disorders frequently occur during the course of the disease despite successful control of inflammation. OBJECTIVE: Possible interrelations between JIA and pain disorders are presented. METHOD: Besides a review of the available literature, a retrospective cohort study was conducted, including 906 patients with a chronic pain disorder with somatic and psychological factors (CPD) and/or a complex regional pain syndrome type I (CRPS I). The frequency of pre-existing rheumatic illnesses was analyzed. RESULTS: The JIA is a risk factor for the development of a CPD. Especially polyarticular, extended oligoarticular, enthesitis-associated JIA and psoriatic arthropathy were found to be significantly associated with an increased risk for developing CPD. In contrast, an increased risk for development of CRPS I was not observed. CONCLUSION: Our study demonstrates JIA to be a risk factor for the development of chronic pain not only as a result from malpositioning or arthrosis but also as a chronic pain disorder (CPD). Further studies are necessary to clarify the relevance of disease activity and duration and also of psychological factors for the pathogenesis.

Pathologic Evaluation of Influenza A H5N8 Infection Outbreaks in Mule Ducks in Bulgaria.

This article outlines pathomorphologic findings of a study involving commercial mule ducks with confirmed influenza A H5N8 infections after a series of outbreaks in Bulgaria. Examinations were carried out after performing necropsy on dead birds from three different age groups (up to 15, 20 to 30, and 40+ days of age) fattened on different farms. Among birds of all ages, gross lesions were present as lesions affecting the heart. Histologically, the myocardium exhibited severe intermyofibrillar edema, moderate to massive hemorrhages, and degenerative changes. All lesions resulted in single or multiple and small to massive myocardial infarctions. Other affected organs included the brain, lungs, liver, spleen, and pancreas. Nonpurulent lymphocytic encephalitis was found postmortem in ducks that had shown prior clinical nervous signs. Among ducks of all ages, a viral antigen in the cardiomyocytes and the epithelium of air capillaries was found through immunohistochemical detection methods. The results of the present study allowed us to conclude that the highly pathogenic avian influenza A H5N8 viral infection may manifest itself as a systemic illness in commercial mule ducks with septicemic lesions, resulting in high morbidity and mortality rates of up to 100%. Pathomorphologic lesions were somewhat different from those previously reported in wild waterfowl.

Evaluación patológica de brotes de infección por influenza A H5N8 en patos mula en Bulgaria. Este artículo describe los hallazgos patomorfológicos de un estudio que involucró patos mula comerciales con infecciones confirmadas de influenza A H5N8 después de una serie de brotes en Bulgaria. Los exámenes se llevaron a cabo después de realizar la necropsia en aves muertas de tres grupos de edad diferentes (hasta 15 días, de 20 a 30 días y más de 40 días de edad) engordadas en diferentes granjas. Entre las aves de todas las edades, las lesiones macroscópicas estaban presentes como lesiones afectando el corazón. Histológicamente, el miocardio exhibió edema intermyofibrillar severo, hemorragias moderadas a masivas y cambios degenerativos. Todas las lesiones resultaron en infartos de miocardio simples o múltiples y de pequeños a masivos. Otros órganos afectados incluyeron el cerebro, los pulmones, el hígado, el bazo y el páncreas. Se encontró encefalitis linfocítica no supurativa se encontró post mortem en patos que habían mostrado signos nerviosos clínicos previos. Entre los patos de todas las edades, se encontró un antígeno viral en los cardiomiocitos y el epitelio de los capilares aéreos a través de métodos de detección inmunohistoquímica. Los resultados del presente estudio nos permitieron concluir que la infección viral altamente patógena de la influenza aviar H5N8 puede manifestarse como una enfermedad sistémica en patos mulos comerciales con lesiones septicémicas, lo que resulta en altas tasas de morbilidad y mortalidad de hasta el 100%. Las lesiones patomorfológicas fueron algo diferentes de las reportadas previamente en aves acuáticas silvestres.

Integrated H∞ filtering bumpless transfer control for switched linear systems.

The integrated H∞ filtering bumpless transfer control problem for switched linear systems is studied in this paper. The target is to attain the H∞ filtering property of the switched linear systems via switchings, while reducing the control bumps induced by switchings. First, a novel description of the bumpless transfer performance is presented, quantifying the suppression level on the control bumps from both relative and absolute viewpoints. Then, a switching logic, a collection of filters and filter-based controllers are jointly designed to attain this target. Further, a criterion which ensures not only the H∞ filtering property but also the bumpless transfer performance is developed. Finally, an application on a turbofan engine control system model is offered, verifying the efficiency of the developed integrated H∞ filtering bumpless transfer control strategy.

Unclear associations between small pelagic fish and jellyfish in several major marine ecosystems.

During the last 20 years, a series of studies has suggested trends of increasing jellyfish (Cnidaria and Ctenophora) biomass in several major ecosystems worldwide. Some of these systems have been heavily fished, causing a decline among their historically dominant small pelagic fish stocks, or have experienced environmental shifts favouring jellyfish proliferation. Apparent reduction in fish abundance alongside increasing jellyfish abundance has led to hypotheses suggesting that jellyfish in these areas could be replacing small planktivorous fish through resource competition and/or through predation on early life stages of fish. In this study, we test these hypotheses using extended and published data of jellyfish, small pelagic fish and crustacean zooplankton biomass from four major ecosystems within the period of 1960 to 2014: the Southeastern Bering Sea, the Black Sea, the Northern California Current and the Northern Benguela. Except for a negative association between jellyfish and crustacean zooplankton in the Black Sea, we found no evidence of jellyfish biomass being related to the biomass of small pelagic fish nor to a common crustacean zooplankton resource. Calculations of the energy requirements of small pelagic fish and jellyfish stocks in the most recent years suggest that fish predation on crustacean zooplankton is 2-30 times higher than jellyfish predation, depending on ecosystem. However, compared with available historical data in the Southeastern Bering Sea and the Black Sea, it is evident that jellyfish have increased their share of the common resource, and that jellyfish can account for up to 30% of the combined fish-jellyfish energy consumption. We conclude that the best available time-series data do not suggest that jellyfish are outcompeting, or have replaced, small pelagic fish on a regional scale in any of the four investigated ecosystems. However, further clarification of the role of jellyfish requires higher-resolution spatial, temporal and taxonomic sampling of the pelagic community.

Anti-enteroviral activity of new MDL-860 analogues: Synthesis, in vitro/in vivo studies and QSAR analysis.

A series of 60 nitrobenzonitrile analogues of the anti-viral agent MDL-860 were synthesized (50 of which are new) and evaluated for their activity against three types of enteroviruses (coxsackievirus B1, coxsackievirus B3 and poliovirus 1). Among them, six diaryl ethers (20e, 27e, 28e, 29e, 33e and 35e) demonstrated high in vitro activity (SI > 50) towards at least one of the tested viruses and very low cytotoxicity against human cells. Compound 27e possesses the broadest spectrum of activity towards all tested viruses in the same way as MDL-860 does. The most active derivatives (27e, 29e and 35e) against coxsackievirus B1 were tested in vivo in newborn mice experimentally infected with 20 MLD50 of coxsackievirus B1. Compound 29e showed promising in vivo activity (protection index 26% and 4 days lengthening of mean survival time). QSAR analysis of the substituent effects on the in vitro cytotoxicity (CC50) and anti-viral activity of the nitrobenzonitrile derivatives was carried out and adequate QSAR models for the anti-viral activity of the compounds against poliovirus 1 and coxsackievirus B1 were constructed.

Pathological Changes in Natural Infection of Pheasants with Highly Pathogenic Avian Influenza A (H5N8) in Bulgaria.

INTRODUCTION: The study of histopathological changes caused by influenza A (H5N8) viral infection in bird species is essential for the understanding of their role in the spread of this highly infectious virus. However, there are few such studies under natural conditions in minor gallinaceous species. This article describes the pathomorphological findings in Colchis pheasants infected naturally with H5N8 during an epizootic outbreak in Bulgaria. MATERIAL AND METHODS: Samples of internal organs of 10 carcasses were collected for histopathological and immunohistochemical evaluation, virus isolation and identification, and nucleic acid detection. RESULTS: Consistent macroscopic findings were lesions affecting the intestine, heart, lung, and pancreas. Congestion and mononuclear infiltrate were common findings in the small intestine, as were necrosis and lymphoid clusters in the lamina propria of the caeca. Congestion with small focal necrosis and gliosis with multifocal nonpurulent encephalitis were observed in the brain. Myocardial interstitial oedema and degenerative necrobiotic processes were also detected. Immunohistological analysis confirmed systemic infection and revealed influenza virus nucleoprotein in all analysed organs. CONCLUSION: Variable necrosis was observed in the brain, liver, trachea, heart, small intestine, and caeca. Viral antigen was commonly found in the brain, heart, lung and trachea. Contact with migrating waterfowls was suspected as a reason for the outbreak.

[Back to school physical education despite rheumatism : Development and testing of a sport scientific-based physical education certification]. / Zurück in den Schulsport trotz Rheuma : Entwicklung und Überprüfung einer sportwissenschaftlich basierten Schulsportbescheinigung.

BACKGROUND: Taking part in physical education is an important element of social participation for children with chronic diseases. Nevertheless, children suffering from rheumatism mostly receive recommendations to stop sport activities either completely or partially, without underlying scientific guidelines. OBJECTIVE: The aim was the development of an IT-tool based on scientific data in order to create individualized recommendations for sport activities plus verification of its practical feasibility. MATERIAL AND METHODS: An interdisciplinary group of experts developed and approved a prototype of the rheumatism and sports compass (Rheuma und Sport Kompass, RSK) based on the literature and own experience. They considered individual health factors and biomechanics of sports functions. The prototype was tested, revised and reconsidered in an interim evaluation. The resulting RSKv1 was evaluated in a clinical observation phase with 61 patients. The results were subsequently incorporated into the final version of RSK during an interdisciplinary decision-making process. This was verified in a feasibility study with a follow-up survey of rheumatic patients with a RSK partial participation certification for physical education including: clinical assessment during 8 lessons of physical education and after 8 lessons of physical education. Teachers rated the RSK online after 8 lessons. The evaluation was descriptive and differences in mean values were tested. RESULTS AND DISCUSSION: In this study 50 patients and 31 teachers were evaluated. The affliction of pain decreased in terms of frequency, amount and duration after physical education with RSK. No worsening in health was reported after participation in sports. The teachers rated the RSK as understandable, practicable and they felt confident to allow the patients to participate in classes. The RSK was rated significantly better than a standard certification text. With the RSK, patients can be advised to safely take part in physical education.

Decreased electrogustometric taste sensitivity in patients with acquired olfactory dysfunction.

BACKGROUND: Cross-modal chemosensory dysfunction between olfaction and gustation is not well known. METHODOLOGY: 180 participants were classified into three groups (60 with olfactory dysfunction, 60 with gustatory dysfunction and 60 healthy controls without chemosensory dysfunction). Olfactory functions were obtained with Sniffin Sticks; gustatory function was measured by suprathreshold gustatory stimuli (taste sprays) and a quasi-threshold measure of taste function (taste strips) for five taste qualities (sweet, salty, sour, bitter and umami). Electric taste threshold was measured using electrogustometry (EGM). In addition, group differences in dietary behaviors were investigated with a specifically designed questionnaire. RESULTS: Patients with olfactory dysfunction had increased electric taste thresholds and decreased scores for the umami taste strip test as compared to healthy controls. Overall there was no major difference between patients with chemosensory dysfunction and healthy controls regarding dietary behaviors, although some patients certainly exhibited dietary problems. Importantly, patients with taste loss, but not patients with smell loss, exhibited a higher degree of depression than controls. CONCLUSION: Patients with olfactory dysfunction showed decreased taste sensitivity which suggested an interaction between the chemical senses taste, trigeminal function, and olfaction. This provides the basis for including both smell and taste psychophysical assessment in clinical practices. In addition, patients with taste loss appeared to suffer most from chemosensory dysfunction.

Synthesis and anti-enterovirus activity of new analogues of MDL-860.

A series of twelve novel compounds, analogues of antiviral agent MDL-860 were synthesized and their antiviral activity was evaluated in vitro against enteroviruses poliovirus 1 (PV1), Coxsackieviruses B1 (CVB1) and Coxsackieviruses B3 (CVB3). Compounds 14, 24 and 25 manifested strong antiviral effects against CVB1 and PV1 (SI values of 405 and 118 for CVB1 and PV1 respectively). In contrast to the wide anti-enteroviral activity of MDL-860, these three compounds were inactive against CVB3. Compounds 14, 24 and 25 along with MDL-860 were tested in vivo in mice infected with CVB1. Marked protective effects of compounds 14 and 24 were established, PI values of 50% and 33.3%, respectively. In addition, almost all of the tested compounds manifested very low toxicity.