Barbituric Acid Derivatives Research Articles

The Synthesis and Application of Chitosan@Ag2O@Mn3O4 Three‐Phase Nanocomposite as a Heterogeneous Catalyst in the Synthesis of 2‐Hydroxynaphthalenepyrimidine Trione

ABSTRACTThe catalyst is often the most expensive element in a chemical process, rather than the reactants or products. Apart from the financial benefits, it is equally crucial to recover and reuse the catalyst to prevent waste and enhance the process's greenness. This study successfully synthesized the new, superior, and recyclable heterogeneous chitosan@Ag2O@Mn3O4 three‐phase nanocatalyst with high surface area and stability using Ag2O and Mn3O4 nanoparticles that stabilized on chitosan by copreparation method and was characterized by Fourier transform infrared (FT‐IR), scanning electron microscopy (SEM), energy dispersive X‐ray (EDX), transmission electron microscopy (TEM), surface mapping (mapping), X‐ray diffraction (XRD), Brunner–Emmett–Teller (BET), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques in detail. Following, the efficiency of the synthesized nanocatalyst in the preparation of 2‐hydroxynaphthalenepyrimidine triones using the reaction of aromatic aldehydes, β‐naphthol, and barbituric acid derivatives was investigated and proved. The advantages of this method include performing reactions at room temperature, green media, short reaction times, and the easy purification of the products.

Crystal Engineering-Driven Sunlight Responsiveness and Flexible Waveguide Transmission.

Here, a barbituric acid derivative containing pyrene rings (DPPT) was successfully synthesized, and two types of crystals were prepared by using crystal engineering methods. Orange sheet-like crystals (DPPT-O, observed in visible light), prepared in a DCM/CH3OH solution, exhibited brittleness and weak fluorescence emission, along with sunlight-induced bending and fracturing. Red needle-like crystals (DPPT-R, also observed in visible light), synthesized in a DCM/CH3CN solution, demonstrated elastic properties, strong fluorescence emission, and excellent optical waveguide performance (with an optical loss coefficient of 0.23-0.30 dB mm-1). Single-crystal data analysis revealed that the stacking arrangement of molecules critically influenced the elasticity of the crystals, while the reaction cavity size regulated the photomechanical properties of the crystals. This study achieved effective control over sunlight responsiveness and flexible optical waveguide transmission for the first time, providing innovative insights for the application of homogeneous organic polycrystalline molecular crystals in this field.

Catalyst- and chromatography-free multi-component domino synthesis of 5-alkyl barbituric acids at room temperature

5-Alkylated barbituric acids are an important class of compounds that constitute the basic moiety of several clinically used hypnotic drugs. Here we report a catalyst-free domino Knoevenagel-Michael addition involving barbituric acid, aldehyde, and N,N-disubstituted aniline in solvent acetonitrile to synthesize 5-alkylated barbituric acid derivatives (72–94% yield) without using any chromatographic separation techniques. The C-4 position of aniline acts as the Michael donor. All the reactions are successfully performed without catalysts, providing an environment-friendly and economical route for the synthesis. Moreover, catalyst-free reactions are less sensitive to air and moisture unlike many metal catalysts, with easy separation of products, and simple operating procedures as there is no need for catalyst weighing, recovery, and removal. A plausible mechanism is also proposed based on control experiments.

Multicomponent synthesis of new barbituric acid derivatives

Multicomponent synthesis of new barbituric acid derivatives

Synthesis and anti-bacterial activity of barbituric acid derivatives

When the viable solve the ents businesses launched penicillin, in the establishment of 19th century vented by Alexander Fleming, a major reduction in the number of deaths caused by bacterial infections was confirmed. Optimists have even noticed an end to the period of bacterial diseases. However, to the request, and frequently improper, applications of antibiotics have resulted in the development of drug-the resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), WHO generated a list of priority pathogens to focus the development of new antibacterial drugs against; MRSA ranked as a high priority. Unfortunately, the development of new antibacterial drugs has progressively declined since the 1980s. In my the research work novel derivatives of Barbituric acid obtained from Methyl propyl malonate and Thiourea give 5-methyl-5-propyl-2-sulfanyl Barbituric Acid [ST-I] it was treated with Alkyl Halides gives 5-methyl-5-propyl-2-sulfanyl Barbituric Acid Derivatives which is converted into resultant compound derivatives of (ST-IA to ST-IE). All the compounds synthesized were confirmed by spectral data and evaluated for their methicillin-resistant Staphylococcus aureus (MRSA) activity Vancomycin was used as standard. The compounds DR-IIA and DR-IID have shown good activity and the remaining show poor activity against bacteria.

Substituent Position Dependent Photophysical Properties of Indole – Barbituric and Thiobarbituric Acid based Molecular Rotors

AbstractA series of 2‐ and 3‐methylindole (MI)‐based barbituric acid (BA) and thiobarbituric acid (TBA) derivatives (2MIBA, 2MITBA, 3MIBA and 3MITBA) in Donor (D)‐π‐Acceptor (A) configuration having strong intramolecular charge transfer (ICT) interactions were synthesized by the simple and efficient route. Methyl substituent at the 2‐ and 3‐ position alters the coplanarity of the DA systems leaving 2MI derivatives as nonplanar whilst 3MI derivatives as planar one and the latter forms an intramolecular hydrogen bond between indole N−H and −C=O of BA or TBA, which facilitates the excited state intramolecular proton transfer (ESIPT) emission in 3MIBA and 3MITBA. Comparing the UV‐visible absorption spectra in the solution phase reveals that the ICT band of 2MITBA and 3MITBA are red‐shifted from the 2MIBA and 3MIBA due to the stronger electron‐accepting nature of C=S than the C=O. Since these molecules exert photo‐induced intramolecular charge transfer followed by a rotation around the bridging methylene group, only weak fluorescence is noted. Nevertheless, in an aggregated state, both 3MIBA and 3MITBA exhibit significant aggregation‐induced enhanced emission (AIEE) characteristics in their THF/water mixture, but the effect is not promising for 2MIBA and 2MITBA. Further, melamine‐3MITBA co‐assembly aided through an intermolecular hydrogen bonding network can also be used as a solid‐state emitter.

Febrile seizures in pediatric practice: Risk factors, clinical manifestations, and intensive therapy

Introduction. Febrile seizures (FS) is the most common type of epileptic seizure experienced by young children. Study of methods of intensive treatment (IT) of FS represents a vital area of research in today’s pediatric science. The aim of this work: to assess the current approaches to risk factors, clinical manifestations and emergency care for patients with FS in pediatric practice. Materials and methods. The authors performed an analysis of publications that were found in the Cochrane Library, PubMed, eLibrary.ru, and Medscape databases using the following search terms: febrile seizures, children and adolescents, intensive treatment, anticonvulsants. A total of 64 published sources were chosen for review. Results and Discussion. The risk factors for FS may be numerous, with the main etiological causes in children being genetic susceptibility, viral infections and vaccination. The clinical presentation of FS is characterized by the development of a generalized tonic-clonic seizure in the setting of a high body temperature (≥39°C). FS are subdivided into three main clinical types: simple, complex and febrile status epilepticus (FSE). History taking and physical examination represent the main diagnostic means for determining the type of FS and discovering the cause of infection. Laboratory tests, electroencephalography, neuroimaging studies and lumbar puncture are used on a limited basis, mainly in children with complicated FS accompanied by a brain infection. Hospitalization for IT is necessary if the child has prolonged febrile seizures or FSE. The drugs of choice for relieving FS are benzodiazepines. Barbituric acid derivatives and valproic acid also possess therapeutic efficacy against FS. Antipyretic agents are effective only in relieving the toxic syndrome, but have no effect on the severity of FS and do not prevent relapses. The main antipyretic medications used for treatment of FS in pediatric practice are paracetamol, ibuprofen and nimesulide. Besides benzodiazepines, IT of FSE involves the use of intravenous fosphenytoin, phenobarbital or levetiracetam. Conclusion. Improvement of the quality of IT in pediatric practice may improve the therapeutic prognosis in patients with FS and bring down complication and mortality rates.

Treatment with a new barbituric acid derivative suppresses diet-induced metabolic dysfunction and non-alcoholic fatty liver disease in mice

IntroductionNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, often accompanied by obesity, diabetes, and increased risks of depression and anxiety. Currently, there are no FDA-approved drugs to treat NAFLD and its related systemic symptoms. Previously, we identified a new barbituric acid derivative (BA-5) that expressed effectiveness against fibrosis and drug-resistant hepatocellular carcinoma. AimsThis study investigated the potential of BA-5 against high-fat diet (HFD)-induced NAFLD and mood disorders in mice. Main methodsSix-weeks-old male C57BL/6 mice were fed with a 45 % HFD for 8 weeks to induce NAFLD and associated metabolic disorders. Mice were treated with a BA-5 and the therapeutic effects and the underlying molecular mechanisms were investigated. Key findingsAdministration of BA-5 significantly reduced serum levels of alanine aminotransferase (ALT), low-density lipoprotein (LDL), fatty acids (FA), and triglycerides (TG) in HFD-fed mice. BA-5 treatment decreased expressions of hepatic lipogenesis-related markers (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and ATP-citrate lyase (ACLY)), increased fatty acid oxidation markers (carnitine palmitoyltransferase 1A (CPT1A) and acyl-CoA oxidase 1 (ACOX1)), and attenuated hepatic fat accumulation in HFD-fed mice. Moreover, HFD-induced adipocyte size enlargement and activation of lipolysis markers such as phosphorylated (p)-hormone-sensitive lipase (HSL) 565, p-HSL 660, and perilipin were inhibited in BA-5-treated mice. Notably, HFD-induced anxiety- and depression-like behaviors significantly improved in the BA-5 treated group through enhanced anti-inflammatory responses in the hippocampus. SignificanceThis study provides new insights into clinical therapeutic strategies of barbituric acid derivatives for HFD-induced NAFLD and associated mood disturbances.

Succinimidium Perchlorate as a Novel and Efficient Brönsted Acidic Ionic Liquid Promoter for the Synthesis of 5-arylidene Barbituric Acid and pyrano[2,3-d] Pyrimidinone Derivatives

Introduction:: In this article, succinimidinium perchlorate as a new acidic ionic liquid catalyst was prepared and used to synthesize 5-arylidene barbituric acid and pyrano[2,3-d]pyrimidinone derivatives. Method:: These two derivatives of barbituric acid have a variety of useful properties. Result:: The advantages of this reagent were high yields, high efficiency, short reaction times, easy performance, easy work-up and reusability. Conclusion:: Succinimidinium perchlorate, which was made for the first time in this project, was identified with different methods, including FT-IR, 1H NMR, 13C NMR and mass spectroscopic techniques

Introduction of a DABCO-Based Ionic Liquid for the Promotion of the Synthesis of Two Important (Thio)barbituric Acid Derivatives

Introduction of a DABCO-Based Ionic Liquid for the Promotion of the Synthesis of Two Important (Thio)barbituric Acid Derivatives

Synthesis and characterization of Co-MOF@Ag2O nanocomposite and its application as a nano-organic catalyst for one-pot synthesis of pyrazolopyranopyrimidines

In this study, a Co-MOF was synthesized via a co-precipitation procedure and then used as support for stabilizing Ag ions and producing Co-MOF@Ag2O nanocomposite by microwave irradiation. The characterization of synthesized Co-MOF@Ag2O nanocomposite was performed by using different techniques such as field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX) analyses, X-ray diffraction (XRD), Thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) and Fourier-transform infrared (FT-IR). The prepared Co-MOF@Ag2O nanocomposite was applied as a heterogeneous nano-catalyst in the synthesis of pyrazolopyranopyrimidines in water at 50 °C via the one-pot multicomponent reaction of ethyl acetoacetate, hydrazine hydrate, aromatic aldehydes and barbituric acid derivatives. Through this straightforward and effective protocol, different tricyclic fused pyrazolopyranopyrimidines were synthesized at high yields, and short reaction times, through an uncomplicated work-up process with no by-product. The Co-MOF@Ag2O nanocomposite has been effectively recycled for four consecutive cycles without appreciable loss in its activity. Cost-effectiveness, no need for column chromatography, mild conditions, catalyst recyclability, and eco-friendly nature make it a promising candidate compared to other methods.

Two-Dimensional Hetero- to Homochiral Phase Transition from Dynamic Adsorption of Barbituric Acid Derivatives.

Barbituric acid derivative (TDPT) is an achiral molecule, and its adsorption on a surface results in two opposite enantiomerically oriented motifs, namely TDPT-Sp and Rp. Two types of building blocks can be formed; block I is enantiomer-pure and is built up of the same motifs (format SpSp or RpRp) whereas block II is enantiomer-mixed and composes both motifs (format SpRp), respectively. The organization of the building blocks determines the formation of different nanoarchitectures which are investigated using scanning tunneling microscopy at a liquid/HOPG interface. Sophisticated, highly symmetric "nanowaves" are first formed from both building blocks I and II and are heterochiral. The "nanowaves" are metastable and evolve stepwisely into more close-packed "nanowires" which are formed from enantiomer-pure building block I and are homochiral. A dynamic hetero- to homochiral transformation and simultaneous multi-scale phase transitions are demonstrated at the single-molecule level. Our work provides novel insights into the control and the origin of chiral assemblies and chiral transitions, revealing the various roles of enantiomeric selection and chiral competition, driving forces, stability and molecular coverage.

Arylidene Meldrum's Acid: A Versatile Structural Motif for the Design of Enzyme-Responsive "Covalent-Assembly" Fluorescent Probes with Tailor-Made Properties.

Latent cyclic C-nucleophiles are recently proving their value in the field of reaction-based fluorescent probes, far beyond their primary utility in organic synthesis. They are typically used to introduce a Michael acceptor moiety acting as a recognition/reaction site for analyte to be detected or as a kinetic promoter of fluorogenic cascade reactions triggered by a reactive species. C-nucleophiles bearing a further reactive handle offer an additional opportunity for tuning the physicochemical/targeting properties or providing drug-releasing capabilities to these probes, through the covalent attachment of ad hoc chemical moiety. In order to implement such strategy to fluorogenic enzyme substrates based on the "covalent-assembly" principle, we have explored the potential of some functionalized derivatives of barbituric acid, piperidine-2,4-dione and Meldrum's acid. Our investigations based on the rational design and validations of enzyme-responsive caged precursors of fluorescent pyronin dyes and 7-(diethylamino)coumarin-3-carboxylic acid, led to identify a versatile candidate suitable for this late-stage structural optimization approach. This Meldrum's acid derivative enables to either enhance water solubility or achieve the reversible conjugation of a targeting ligand, while promoting in situ formation of fluorophore upon enzymatic activation. This study opens the way to novel multifunctional fluorescence imaging probes and optically modulated small conjugate-based theranostics.

Water mediated pot, atom, and step economic (PASE) synthesis of pyrimido[4,5-d]pyrimidines using ultrasound and microwave irradiation approaches

The functioning, Pot, Atom, and Step Economic (PASE) green chemistry proposition has been approached for the synthesis of pyrimido[4,5-d]pyrimidines by the multicomponent reaction (MCR) of barbituric acid, guanidine, and aldehyde derivatives using water solvent and iodine catalyst through ultrasound and microwave irradiation methods. Reaction optimization was performed by varying solvents, reaction time, the concentration of catalyst, and reaction methods. Microwave irradiation approach using water solvent and iodine catalyst (8 mol%) with 5 min led to offer the highest yield. EWG substituted compound 4 g (4-NO2, guanidine) [87% (U.S.), 93% (M.W.)] was found to be the highest yielded compound in this study. The greenness of the reaction was estimated by calculating some green chemistry metrics. The metrics approved the proposed protocol as an ideal, green, and sustainable approach.

Design, synthesis and characterization of some new pyrazol-pyrimidine derivatives and evaluation of their biological activities

In this work, we have reported a synthesis of some novel pyrazol-pyrimidine derivatives (3a-f) obtained by the reaction of substituted pyrazole aldehydes and barbituric acid derivatives in presence of L-proline as a catalyst via Knoevengal condensation reaction. The structures of the synthesized compounds were characterized by spectral methods. From antibacterial activity, compounds 3d and 3f exhibited highest zone of inhibition as compared to standard drug gentamicin. Cytotoxicity results revealed that compound 3e exhibited a promising IC50 value against both the cell lines (A549 and MCF-7) as compared to the standard drug doxorubicin. Docking study discloses that, all the newly synthesized compounds displayed promising binding energies with the protein receptor EGFR kinase domain.

Structural Analysis of Calcium Oxide Derived from Waste Egg’s Shells and their Application for Knoevenagel Condensation Reactions

The present study demonstrates the simple and easy synthesis of calcium oxide (CaO) from waste egg’s shells. Fine egg’s shells powder were calcinated at 500, 700 and 800 ºC. The structural and morphological evaluation of calcium oxide derived from waste egg’s shell were examined by using XRD, FT-IR, SEM, EDS and TEM techniques. The sintered calcium oxide was used as heterogeneous catalyst for the synthesis of 5-arylidene malononitrile and 5-arylidene barbituric acid derivatives by the condensation of various aromatic aldehyde and active methylene compounds via Knoevenagel condensations reaction under ultrasound irradiation method. The reaction completed within a very short reaction time with high yields of product. The present method describes easy synthesis of calcium oxide catalyst from the waste egg’s shells, short reaction times, simple product isolation, excellent yield and reusability of the catalyst.

Acute poisoning with ваrbituric acid derivatves. Barbituric coma

Introduction. Aim of the study. To summarize the authors’ many years of experience in the diagnosis and treatment of acute poisoning with barbituric acid derivatives and to present the results of a detailed study of the clinic of barbituric intoxication, which prove a toxic damaging effect on the body, causing a deep inhibition of the functions of the central nervous system (CNS) with a predominant effect on the cortex and autonomic centers of the brain trunk. Material and methods. The analysis of 385 patients with acute poisoning with barbiturates of varying severity who were treated in the emergency toxicology department of the N.V. Sklifosovsky Research Institute for Emergency Medicine was carried out. The clinical and encephalographic picture of acute poisoning was assessed. The EEG data of two groups of patients were considered and analyzed, with the possibility of determining the type of bioelectric activity of the brain. The informative value of these types of EEG for a physician is in comparison with the characteristics of clinical and toxicological data. Results. Summarizing the obtained results of clinical and electroencephalographic changes in barbiturate poisoning, it was noted that the identified types of brain bioelectrical activity correspond to certain clinical symptoms and indicate different degrees of poisoning severity. This makes it possible for a practicing physician, after recording an EEG in a patient in a coma, to make a preliminary diagnosis of acute barbiturate poisoning, to purposefully conduct a toxicological study, and to begin specific treatment before receiving an analysis. Analeptic bemegrid causes a direct stimulating effect on the central nervous system. With the introduction of small doses of bеmegrid, a moderate activation of the bioelectrical activity of the brain was noted. Our experience in treating patients with this poisoning showed a negative effect of large doses of bemegrid on the central nervous system, which can lead to an inhibitory phase of parabiotic inhibition (according to N.E. Vvedensky). Conclusion. Poisoning with barbituric acid derivatives currently poses a serious danger to the life and health of patients. This makes the issue of timely diagnosis and treatment measures in the early stages of the disease relevant.

Green Synthesis of Dihydropyrimido[4,5‐b]quinolinetriones by Sulfonic Acid‐Functionalized Silica‐Coated CoFe2O4 as a Solid Acid Nanocatalyst under Thermal and Ultrasonic Conditions

AbstractSulfonic acid functionalized silica coated cobalt ferrite nanoparticles (CoFe2O4/SiO2−SO3H) was prepared as an efficient solid acid catalyst for the green synthesis of dihydropyrimido[4,5‐b]quinolinetrione derivatives. CoFe2O4 NPs were prepared by co‐precipitation method and then the silica‐coated CoFe2O4 NPs were modified with chlorosulfonic acid. Obtained CoFe2O4/SiO2−SO3H was characterized by thermo gravimetric analysis (TGA), Fourier transform‐infrared spectroscopy (FT‐IR), scanning electron microscope (SEM), energy‐dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD) and vibrating‐sample magnetometer (VSM). The magnetically separable CoFe2O4/SiO2−SO3H was successfully used for the four component reaction of barbituric acid, dimedone, amines (or ammonium acetate) and benzaldehyde derivatives for the synthesis of dihydropyrimido[4,5‐b]quinolinetriones under thermal and ultrasound conditions. The advantages of presented simple protocol are the easily separation of magnetic catalyst from the reaction medium by an external magnet, short reaction times, green reaction conditions in addition to simple workup and high yield of products.

QSRR DESCRIPTORS AS A TOOL IN THE STUDY OF THE BARBITURIC ACID DERIVATIVES’ BIOLOGICAL PROFILE

Thanks to the in silico approach in drug design, the identification of new molecules is enabled and facilitated, as well as the optimization of the pharmacokinetics and toxicity of compounds obtained from different sources. Chromatographic methods, on the other hand, provide accurate and reliable information on the influence of the nature of substituents and applied organic modifiers on the pharmacological behavior of compounds, relying on the existence of similarities between intermolecular interactions that determine compound behavior in biological and chromatographic media. Barbituric acid derivatives were subjected to QSRR analysis and the parameters obtained by reversed phase thin layer chromatography (RP TLC18 F254s) were correlated with selected software-derived predictors of permeability, pharmacokinetics and toxicity using the method of linear regression. Тhus satisfactory mathematical models were obtained.

Microwave-assisted synthetic method of novel Bi2O3 nanostructure and its application as a high-performance nano-catalyst in preparing benzylidene barbituric acid derivatives.

In this study, controllable and optimal microwave irradiation has been used to synthesize the novel nanostructures of Bi2O3 under environmental conditions. The final products had a thermal stability of 210°C, an average particle size distribution of 85 nm, and a surface area of 783 m2/g. The high thermodynamic stability of Bi2O3 nanostructures was confirmed by TG and differential scanning calorimetry (DSC) analyses. The nanostructure nature of compounds, and most importantly, the use of an effective, cost-effective, and rapid synthesis route of microwave have created significant physiochemical properties in the Bi2O3 products. These unexpected properties have made the possibility of potential application of these products in various fields, especially in nano-catalyst applications. It is well-documented that, as Lewis acid, bismuth nano-catalyst exhibits a great catalytic activity for the green synthesis of some bio-active barbituric acid derivatives using precursors with electron-donating or electron-withdrawing nature in high yields (80%–98%). After incorporating this catalyst into the aqueous media, all the reactions were completed within 2–3 min at room temperature. The main advantages of this method are practical facility, the availability of starting materials, and low costs besides the catalyst reusability. Additionally, the catalyst synthesis process may be carried out in the aqueous media for a short period with medium to high yields. The obtained results have opened a new window for the development of a novel nano-catalyst with practical application.