Novel Substituted Azoloazines with Anticoagulant Activity
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
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Novel Substituted Azoloazines with Anticoagulant Activity
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| Автор |
Spasov, A. A.
Fedorova, O. V. Rasputin, N. A. Ovchinnikova, I. G. Ishmetova, R. I. Ignatenko, N. K. Gorbunov, E. B. Sadykhov, G. A. O. Kucheryavenko, A. F. Gaidukova, K. A. Sirotenko, V. S. Rusinov, G. L. Verbitskiy, E. V. Charushin, V. N. |
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| Тематика |
1,2,4-TRIAZOLO[5,1-C]TRIAZINES
ANTICOAGULANT AZOLO[1,2,4,5]TETRAZINES AZOLO[1,5-A]PYRIMIDINES CYTOKINE STORM INDOLO[2,3-B]QUINOXALINES 2 CYCLOPENTYLTHIO 6 NITRO 7 METHOXY 4,7 DIHYDRO[1,5 A]PYRIMIDYL 4 GUANIDATE 2 TRIFLUOROMETHYL 6 NITRO 7 METHOXY 4,7 DIHYDRO[1,5 A]PYRIMIDYL 4 GUANIDATE 3 GUANIDINO 6 ALKYLTHIOIMIDAZO[1,2 B][1,2,4,5]TETRAZINE DERIVATIVE 4 [7 (THIOPHEN 2 YL)[1,2,4]TRIAZOLO[1,5 A]PYRIMIDIN 5 YL]ANILINE 4,4' (IMIDAZO[1,2 A]PYRIMIDINE 5,7 DIYL)DIANILINE 4,5 DIHYDRO[1,2,4]TRIAZOLO[1,5 A]PYRIMIDINE DERIVATIVE 6 GUANIDINO 3 ALKYLTHIO[1,2,4]TRIAZOLO[4,3 B][1,2,4,5]TETRAZINE DERIVATIVE 6 GUANIDINO 3 CYCLOPENTYLTHIO[1,2,4]TRIAZOLO[4,3 B][1,2,4,5]TETRAZINE 6 GUANIDINO 3 OCTYLTHIO[1,2,4]TRIAZOLO[4,3 B][1,2,4,5]TETRAZINE 6 NITRO 7 HYDROXY 4,7 DIHYDRO 1,2,4 TRIAZOLO[5,1 C ]TRIAZINYL 4 GUANIDATE ANTICOAGULANT AGENT ANTITHROMBIN DABIGATRAN ETEXILATE ECARIN ETHYL 7 [3 (2 AMINOACETAMIDO)PHENYL] 5 METHYL 4,7 DIHYDRO[1,2,4]TRIAZOLO[1,5 A]PYRIMIDINE 6 CARBOXYLATE ETHYL 7 [4 (2 AMINOACETAMIDO)PHENYL] 5 METHYL 4,7 DIHYDRO[1,2,4]TRIAZOLO[1,5 A]PYRIMIDINE 6 CARBOXYLATE INDOLO[2,3 B]PYRAZINE DERIVATIVE PYRIMIDINE DERIVATIVE UNCLASSIFIED DRUG ANTICOAGULANT AGENT ANTIDIABETIC AGENT ANTIVIRUS AGENT DABIGATRAN ACTIVATED PARTIAL THROMBOPLASTIN TIME ANIMAL EXPERIMENT ANIMAL MODEL ANIMAL TISSUE ANTICOAGULATION ANTIDIABETIC ACTIVITY ARTICLE BIGINELLI REACTION BLOOD CLOTTING TIME BROMINATION BUCHWALD HARTWIG CROSS COUPLING REACTION CARBON NUCLEAR MAGNETIC RESONANCE CONTROLLED STUDY CROSS COUPLING REACTION CYTOKINE STORM DRUG IDENTIFICATION DRUG SYNTHESIS EC50 IC50 IN VITRO STUDY LEPORIDAE MALE NONHUMAN PROTHROMBIN TIME PROTON NUCLEAR MAGNETIC RESONANCE RAT STRUCTURE ACTIVITY RELATION SUBSTITUTION REACTION THROMBIN TIME CORONAVIRUS DISEASE 2019 HUMAN ANTICOAGULANTS ANTIVIRAL AGENTS COVID-19 DABIGATRAN HUMANS HYPOGLYCEMIC AGENTS |
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| Описание |
Hypercytokinemia, or cytokine storm, often complicates the treatment of viral and bacterial infections, including COVID-19, leading to the risk of thrombosis. However, the use of currently available direct anticoagulants for the treatment of COVID-19 patients is limited due to safety reasons. Therefore, the development of new anticoagulants remains an urgent task for organic and medicinal chemistry. At the same time, new drugs that combine anticoagulant properties with antiviral or antidiabetic activity could be helpfull in the treatment of COVID-19 patients, especially those suffering from such concomitant diseases as arterial hypertension or diabetes. We have synthesized a number of novel substituted azoloazines, some of which have previously been identified as compounds with pronounced antiviral, antibacterial, antidiabetic, antiaggregant, and anticoagulant activity. Two compounds from the family of 1,2,4-triazolo[1,5-a]pyrimidines have demonstrated anticoagulant activity at a level exceeding or at least comparable with that of dabigatran etexilate as the reference compound. 7,5-Di(2-thienyl)-4,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine has shown the highest ability to prolong the thrombin time, surpassing this reference drug by 2.2 times. This compound has also exhibited anticoagulant activity associated with the inhibition of thrombin (factor IIa). Moreover, the anticoagulant effect of this substance becomes enhanced under the conditions of a systemic inflammatory reaction. © 2023 by the authors.
Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-777 This research was funded by the Ministry of Science and Higher Education of the Russian Federation (agreement on the provision of grants from the federal budget in the form of subsidies under paragraph 4 of article 78.1 of the Budget Code of the Russian Federation, Moscow, 1 October 2020, no. 075-15-2020-777). |
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| Дата |
2024-04-05T16:35:52Z
2024-04-05T16:35:52Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Spasov, A, Fedorova, O, Rasputin, N, Ovchinnikova, I, Ishmetova, R, Ignatenko, N, Gorbunov, E, Sadykhov, G, Kucheryavenko, A, Gaidukova, K, Sirotenko, VS, Rusinov, GL, Verbitskiy, E & Charushin, V 2023, 'Novel Substituted Azoloazines with Anticoagulant Activity', International Journal of Molecular Sciences, Том. 24, № 21, 15581. https://doi.org/10.3390/ijms242115581
Spasov, A., Fedorova, O., Rasputin, N., Ovchinnikova, I., Ishmetova, R., Ignatenko, N., Gorbunov, E., Sadykhov, G., Kucheryavenko, A., Gaidukova, K., Sirotenko, V. S., Rusinov, G. L., Verbitskiy, E., & Charushin, V. (2023). Novel Substituted Azoloazines with Anticoagulant Activity. International Journal of Molecular Sciences, 24(21), [15581]. https://doi.org/10.3390/ijms242115581 1661-6596 Final All Open Access, Gold, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85176322723&doi=10.3390%2fijms242115581&partnerID=40&md5=57c29372a6ef5a898df667f5a2fd5e50 https://www.mdpi.com/1422-0067/24/21/15581/pdf?version=1698235588 http://elar.urfu.ru/handle/10995/130943 10.3390/ijms242115581 85176322723 |
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| Язык |
en
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| Права |
Open access (info:eu-repo/semantics/openAccess)
cc-by https://creativecommons.org/licenses/by/4.0/ |
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| Формат |
application/pdf
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| Издатель |
Multidisciplinary Digital Publishing Institute (MDPI)
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| Источник |
International Journal of Molecular Sciences
International Journal of Molecular Sciences |
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