Synthesis of 1,2,4-Oxadiazin-5(6)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors.

Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson's disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6)-ones.

Application of the intramolecular Diels-Alder vinylarene (IMDAV) reaction for the synthesis of benzo-, carbocyclo-, thienothiopheneisoindolecarboxylic acids and its limitations.

Thienylallylamines, readily accessible from the corresponding thienyl aldehydes, react with maleic and trifluoromethylmaleic anhydrides leading to the formation of acids with a thieno[2,3-]isoindole core. The reaction sequence involves two successive steps: acylation of the nitrogen atom of the initial allylamine and the intramolecular Diels-Alder vinylarene (IMDAV) reaction. The scope and limitations of the proposed method were thoroughly investigated.

Room Temperature Synthesis of Bioactive 1,2,4-Oxadiazoles.

1,2,4-Oxadiazole is an essential motif in drug discovery represented in many experimental, investigational, and marketed drugs. This review covers synthetic methods that allow the conversion of different types of organic compounds into 1,2,4-oxadiazole at ambient temperature and the practical application of the latter approaches for the preparation of pharmaceutically important molecules. The discussed methods are divided into three groups.

Monoamine oxidase inhibition properties of 2,1-benzisoxazole derivatives.

Monoamine oxidase (MAO) are flavoenzymes that metabolize neurotransmitter, dietary and xenobiotic amines to their corresponding aldehydes with the production of hydrogen peroxide. Two isoforms, MAO-A and MAO-B, are expressed in humans and mammals, and display different substrate and inhibitor specificities as well as different physiological roles. MAO inhibitors are of much therapeutic value and are used for the treatment of neuropsychiatric and neurodegenerative disorders such as depression, anxiety disorders, and Parkinson's disease.

Unusual Formation of 1,2,4-Oxadiazine Core in Reaction of Amidoximes with Maleic or Fumaric Esters.

We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4-1,2,4-oxadiazin-5(6)-ones.

Design of 4-Substituted Sulfonamidobenzoic Acid Derivatives Targeting Coxsackievirus B3.

A series of novel 4-substituted sulfonamidobenzoic acid derivatives was synthesized as the structural evolution of 4-(4-(1,3-dioxoisoindolin-2-yl)phenylsulfonamido)benzoic acid, which is the known inhibitor of the enterovirus life cycle. Antiviral properties of prepared compounds were evaluated using phenotypic screening and viral yield reduction assay. Their capsid binding properties were verified in thermostability assay.

External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains.

A new route to 5-amino-1,2,4-thiadiazole derivatives via reaction of N-chloroamidines with isothiocyanates has been proposed. The advantages of this method are high product yields (up to 93%), the column chromatography-free workup procedure, scalability and the absence of additive oxidizing agents or transition metal catalysts. The 28 examples of 5-amino-1,2,4-thiadiazole derivatives obtaining via the proposing protocol were evaluated in vitro against ESKAPE pathogens strains (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae).

Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes.

Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs ([Cu(L)Cl][Cl] or (Cu()Cl) depending on the substitution pattern on the 2-pyridine fragment were revealed. In addition, antiproliferative action of the obtained compounds have been investigated against lung cancer cell lines (A549, NCI-H460, NCI-H1975), and healthy WI-26 VA4 cells were used to monitor non-specific cytotoxicity.

π-π Noncovalent Interaction Involving 1,2,4- and 1,3,4-Oxadiazole Systems: The Combined Experimental, Theoretical, and Database Study.

A series of -pyridyl ureas bearing 1,2,4- (, , and ) and 1,3,4-oxadiazole moiety (, , ) was prepared and characterized by HRMS, H and C NMR spectroscopy, as well as X-ray diffraction. The inspection of the crystal structures of (-), and the Hirshfeld surface analysis made possible the recognition of the (oxadiazole)···(pyridine) and (oxadiazole)···(oxadiazole) interactions. The presence of these interactions was confirmed theoretically by DFT calculations, including NCI analysis for experimentally determined crystal structures as well as QTAIM analysis for optimized equilibrium structures.

Comparative Structural Study of Three Tetrahalophthalic Anhydrides: Recognition of X···O(anhydride) Halogen Bond and πh···O(anhydride) Interaction.

Structures of three tetrahalophthalic anhydrides (TXPA: halogen = Cl (TCPA), Br (TBPA), I (TIPA)) were studied by X-ray diffraction, and several types of halogen bonds (HaB) and lone pair···π-hole (lp···πh) contacts were revealed in their structures. HaBs involving the central oxygen atom of anhydride group (further X···O(anhydride) were recognized in the structures of TCPA and TBPA. In contrast, for the O(anhydride) atom of TIPA, only interactions with the π system (π-hole) of the anhydride ring (further lp(O)···πh) were observed.

The influence of different modes of ventilation on standing balance of athletes.

Background: The respiratory movements are one of the factors influencing standing balance. Although well-trained athletes have better postural performance compared to untrained men, it's not quite clear, if the formers' upright posture would be more stable during different ventilation modes, maximal voluntary hyperventilation and inspiratory breath-holding. There are no studies on this subject in the available literature.