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Information × Registration Number 0221U105717, 0117U004134 , R & D reports Title Synthesis, structure, properties and molecular mechanisms of action of new antithrombotic and antiviral agents. popup.stage_title Head Andronati Sergii A., д.х.н. Registration Date 17-08-2021 Organization Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine popup.description2 Aim of the study: To perform molecular docking and to study the effect of 2-(piperazin-1-yl) quinazoline derivatives on the specific binding of FITC-fibrinogen to ІІb3. Construction of SAR or QSAR model and prediction of structures of ІІb3 inhibitors. Implementation of methods for building "self-consistent" QSAR models and assessment of their areas of competence. Evaluation of the effectiveness of these techniques on samples of biologically active compounds. Synthesis of predicted structures of potential interferon inducers. The affinity of 2-(piperazin-1-yl)quinazoline derivatives for the fibrinogen receptor (ІІb3) was studied. The test compounds inhibit the binding of fibrinogen to αIIbβ3 with IC50 values from 30 μM to 0.6 μM. The main binding centers of 2-(piperazin-1-yl) quinazoline derivatives to ІІb3 were established by the molecular docking method. Based on 4-aminoacetophenone, 2-(3,4-diaminophenyl) ethylamines were first obtained, which are key "building blocks" for the design of potential DNA intercalators. Based on the corresponding methyl derivatives, a series of 6- and 7-dialkylaminomethyldenoquinoxalinones and 9-dialkylaminomethylindoloquinoxalines were obtained by sequential bromination and amination. Based on the method of displacing ethidium bromide from its complex with DNA, the association constants of indeno- and indolo-quinoxaline derivatives were obtained. These compounds belong to medium strength DNA intercalators with lgK = 5 - 6. The effect of structure on immunostimulatory activity (neutrophil activation) was studied for a number of substituted indoloquinoxalines (41 compounds). Due to the use of information-simplex descriptors and the procedure of self-coordination of "structure-activity" models, adequate 2D-QSAR models with high predictive power were built (R2 test = 0.91 - 0.93). The key role of lipophilicity of molecules and each substituent R1 - R9 is revealed, the direction and degree of influence on activity are determined. As Product Description popup.authors Illyushko Natalia О. Andronati Serhii А. Kabanova Tetiana A. Karpenko Oleksandr S. Kornylov Oleksandr Yu. Krysko Andrii А. Krysko Olga L. Kuzmin Victor Evgenovich Lyakhov Sergii A. Mikhaylova Tetiana V. Shibinska Marina O. popup.nrat_date 2021-08-17 Close