4-Alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline Derivatives as New Heterocyclic Analogues of Indolo[2,3-]quinoxalines: Synthesis and Antitubercular Activity.

The synthetic approach based on a sequence of Buchwald-Hartwig cross-coupling and annulation through intramolecular oxidative cyclodehydrogenation has been used for the construction of novel 4-alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline derivatives. For the first time, these polycyclic compounds were evaluated for antimycobacterial activity, including extensively drug-resistant strains. A reasonable bacteriostatic effect against HRv was demonstrated.

Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease.

New conjugates of amiridine and salicylic derivatives (salicylamide, salicylimine, and salicylamine) with different lengths of alkylene spacers were designed, synthesized, and evaluated as potential multifunctional central nervous system therapeutic agents for Alzheimer's disease (AD). Conjugates demonstrated high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition (IC: AChE, 0.265-4.

Azolopyrimidine-Based Thioethers: Synthesis via Cross-Dehydrogenative C-S Coupling and In Silico Evaluation of Anti-SARS-CoV-2 Activity.

Azoloazine derivatives are known as promising small molecules that are potentially able to counteract a broad spectrum of RNA viruses including SARS-CoV-2. However, a pool of synthetic pathways to provide convenient structural modification of such compounds without de novo construction of the heterocyclic scaffold is rather limited so far. This work proposes an approach to the direct C(sp)-H functionalization of azolopyrimidine substrates with aromatic thiol residues, mediated by the iodine/persulfate reagent system.

2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropanoic acids as selective and effective carboxylesterase inhibitors with powerful antioxidant potential.

A series of 2-arylhydrazinylidene-3-oxo acids (AHOAs) was prepared by dealkylation of alkyl-2-arylhydrazinylidene-3-oxo-3-alkanoates with AlBr. Using X-Ray, NMR spectroscopy, and quantum mechanical calculations (QM), the existence of AHOAs in a thermodynamically favorable Z-form stabilized by two intramolecular H-bonds was established. All AHOAs had acceptable ADME parameters.

Design, Synthesis, and Photophysical Properties of 5-Aminobiphenyl Substituted [1,2,4]Triazolo[4,3-]- and [1,2,4]Triazolo[1,5-]quinazolines.

Two series of novel [1,2,4]triazolo[4,3-]- and [1,2,4]triazolo[1,5-]quinazoline fluorophores with 4'-amino[1,1']-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-]-annulated triazoloquinazolines, whereas [1,5-] isomers are formed in acidic media as a result of Dimroth rearrangement. A 1D-NMR and 2D-NMR spectroscopy, as well as a single-crystal X-ray diffraction analysis, unambiguously confirmed the annelation type and determined the molecular structure of -bromophenyl intermediates and target products.

Quinazolines annelated at the N(3)-C(4) bond: Synthesis and biological activity.

This review covers article and patent data obtained mostly within the period 2013-2023 on the synthesis and biological activity of quinazolines [c]-annelated by five- and six-membered heterocycles. Pyrazolo-, benzimidazo-, triazolo- and pyrimido- [c]quinazoline systems have shown multiple potential activities against numerous targets. We highlight that most research efforts are directed to design of anticancer and antibacterial agents of azolo[c]quinazoline nature.

Iodine-Catalyzed Radical C-H Amination of Nonaromatic Imidazole Oxides: Access to Cyclic α-Aminonitrones.

A straightforward cross-dehydrogenative coupling approach to incorporate alicyclic amino residues into the structure of model cyclic aldonitrones, 2-imidazole oxides, is reported. The elaborated C(sp)-H functionalization is achieved by employing cyclic amines in the presence of the I--butyl hydroperoxide (TBHP) reagent system. As a result, a series of 19 novel heterocyclic derivatives were obtained in yields of up to 97%.

Conjugates of amiridine and thiouracil derivatives as effective inhibitors of butyrylcholinesterase with the potential to block β-amyloid aggregation.

New amiridine-thiouracil conjugates with different substituents in the pyrimidine fragment (R = CH , CF Н, CF , (CF ) H) and different spacer lengths (n = 1-3) were synthesized. The conjugates rather weakly inhibit acetylcholinesterase (AChE) and exhibit high inhibitory activity (IC up to 0.752 ± 0.

Synthesis and Assessment of Antiplatelet and Antithrombotic Activity of 4-Amino-Substituted 5-Oxoproline Amides and Peptides.

Venous thromboembolism is a serious problem because it significantly increases the risk of developing vascular complications in elderly patients with obesity or immobilization, cancer, and many other diseases. Thus, there is a need to study new therapeutic strategies, including new medicinal agents for the efficient and safe correction of thrombus disorders. In this work, we have synthesized a number of new amides and peptides of 4-amino-5-oxoprolines and studied their antiplatelet and antithrombotic activity in experiments in vitro and in vivo.

Derivatives of 9-phosphorylated acridine as butyrylcholinesterase inhibitors with antioxidant activity and the ability to inhibit β-amyloid self-aggregation: potential therapeutic agents for Alzheimer's disease.

We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results.

(1-(4-(5-Phenyl-1,3,4-oxadiazol-2-yl)phenyl)-1-1,2,3-triazol-4-yl)-methylenyls α,ω-Bisfunctionalized 3- and 4-PEG: Synthesis and Photophysical Studies.

Two new azaheterocycle-based bolas, such as (1-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)-1-1,2,3-triazol-4-yl)-methylenyls α,ω-bisfunctionalized PEGs, were prepared via Cu-catalyzed click reaction between 2-(4-azidophenyl)-5-(aryl)-oxadiazole-1,3,4 and terminal ethynyls derived from PEG-3 and PEG-4. Due to the presence of two heteroaromatic cores and a PEG linker, these bola molecules are considered as promising fluorescent chemosensors for electron-deficient species. As a result of a well-pronounced "turn-off" fluorescence response towards common nitro-explosive components, such as 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT), hard-to-detect pentaerythritol tetranitrate (PETN), as well as Hg cation was observed.

3-Aryl-5-aminobiphenyl Substituted [1,2,4]triazolo[4,3-]quinazolines: Synthesis and Photophysical Properties.

Amino-[1,1']-biphenyl-containing 3-aryl-[1,2,4]triazolo[4,3-]quinazoline derivatives with fluorescent properties have been designed and synthesized. The type of annelation of the triazole ring to the pyrimidine one has been unambiguously confirmed by means of an X-ray diffraction (XRD) method; the molecules are non-planar, and the aryl substituents form the pincer-like conformation. The UV/Vis and photoluminescent properties of target compounds were investigated in two solvents of different polarities and in a solid state.

Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO.

Mesomeric Betaines Based on Adamantylated 1,2,4-Triazolo[4,3-a]pyrimidin-5-ones: Synthesis, Structure and Conversion into Anionic N-Heterocyclic Carbenes.

The C-N coupling of 1,2,4-triazolo[1,5-a]pyrimidin-7-ones with 1-adamantanol/1-bromoadamantane leads to 1,2,4-triazolo[4,3-a]pyrimidinium-5-olates, which are represented as mesomeric betaines (MBs). The formation of MBs involves not only N-alkylation of heterocyclic framework but also the rearrangement leading to a change in the type of fusion between pyrimidine and 1,2,4-triazole fragments. The structures of the obtained products were confirmed by the X-ray analysis and measurements of C- C (J ) coupling constants in the 1D C NMR spectra of selectively C-labeled samples.

Triazavirin-A Novel Effective Antiviral Drug.

This review outlines the data of numerous studies relating to the broad-spectrum antiviral drug Triazavirin that was launched on the Russian pharmaceutical market in 2014 as an anti-influenza drug (the international non-patented name is Riamilovir). The range of antiviral activity of Triazavirin has been significantly expanded during recent years; in particular, it has been shown that Triazavirin exhibits activity against tick-borne encephalitis, Rift Valley fever, West Nile fever, and other infections of viral etiology. This drug has been approved for treatment of influenza and acute respiratory infections by the Russian Ministry of Health on the basis of comprehensive clinical trials involving over 450 patients.

Carborane-Containing Folic Acid -Amides: Synthesis and In Vitro Evaluation of Novel Promising Agents for Boron Delivery to Tumour Cells.

The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new - and -carborane-containing folic acid -amides containing 18-20 boron atoms per molecule. Folic acid derivatives containing -carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.

Effect of the Silica-Magnetite Nanocomposite Coating Functionalization on the Doxorubicin Sorption/Desorption.

A series of new composite materials based on FeO magnetic nanoparticles coated with SiO (or aminated SiO) were synthesized. It has been shown that the use of -(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures the increased content of a SiO phase in the FeO@SiO nanocomposites (NCs) in comparison with materials obtained under similar conditions, but without PMIDA. It has been demonstrated for the first time that the presence of PMIDA on the surface of NCs increases the level of Dox loading due to specific binding, while surface modification with 3-aminopropylsilane, on the contrary, significantly reduces the sorption capacity of materials.

Push-Pull Structures Based on 2-Aryl/thienyl Substituted Quinazolin-4(3)-ones and 4-Cyanoquinazolines.

Design and synthesis of 2-(aryl/thiophen-2-yl)quinazolin-4(3)-ones and 4-cyano-2-arylquinazolines with EtN-, PhN- or carbazol-9-yl- electron donating fragment are described. The key photophysical properties of these compounds have been studied by UV/Vis absorption and fluorescence spectroscopy in solvents of different polarity (toluene and MeCN). 2-(Aryl/thiophen-2-yl)quinazolin-4(3)-ones show fluorescence in blue-green region in toluene solution with quantum yields up to 89% in the case of 2-(4'-N,N-diphenylamino[1,1'-biphenyl]-4-yl)-quinazolin-4(3)-one.

Mechanism, Kinetics and Thermodynamics of Decomposition for High Energy Derivatives of [1,2,4]Triazolo[4,3-][1,2,4,5]tetrazine.

This paper presents the data of research studies on the mechanisms, kinetics and thermodynamics of decomposition of three high-energy compounds: [1,2,4]triazolo[4,3-][1,2,4,5]tetrazine-3,6-diamine (TTDA), 3-amino-6-hydrazino[1,2,4]triazolo[4,3-][1,2,4,5]tetrazine (TTGA) and 3,6-dinitroamino[1,2,4]triazolo[4,3-][1,2,4,5]tetrazine (DNTT). The points of change of the reaction mechanisms under thermal effects with different intensities from 0.1 to 2000 s have been established.

Random Copolymers of Styrene with Pendant Fluorophore Moieties: Synthesis and Applications as Fluorescence Sensors for Nitroaromatics.

Five random copolymers comprising styrene and styrene with pendant fluorophore moieties, namely pyrene, naphthalene, phenanthrene, and triphenylamine, in molar ratios of 10:1, were synthesized and employed as fluorescent sensors. Their photophysical properties were investigated using absorption and emission spectral analyses in dichloromethane solution and in solid state. All copolymers possessed relative quantum yields up to 0.

Folic Acid Antimetabolites (Antifolates): A Brief Review on Synthetic Strategies and Application Opportunities.

Antimetabolites of folic acid represent a large group of drugs and drug candidates, including those for cancer chemotherapy. In this current review, the most common methods and approaches are presented for the synthesis of therapeutically significant antimetabolites of folic acid, which are Methotrexate (MTX), Raltitrexed (Tomudex, ZD1694), Pralatrexate, Pemetrexed, TNP-351, and Lometrexol. In addition, the applications or uses of these folic acid antimetabolites are also discussed.