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Synthesis and study of antiplatelet and antithrombotic activity of 4-substituted pyroglutamic acids

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Abstract

A series of (2S,4S)-4-amino-N-arylpyroglutamic acids was first obtained by the nucleophilic substitution of bromine atom in dimethyl (2S,4RS)-4-bromo-N-phthaloylglutamate under the action of primary arylamines, followed by the separation of diastereomers and removal of protecting groups by acidic hydrolysis. These compounds were studied for anti-platelet and antithrombotic activity in experiments in vitro and in vivo. Some compounds were identified as exhibiting a significant effect on platelet function, which was manifested in slowing down the process of thrombus formation in the model of arterial and deep vein thrombosis. It was established that the most efficient compound is (2S,4S)-4-amino-N-(4-fluoro-phenyl)pyroglutamic acid, with its effect being comparable to that of acetylsalicylic acid.

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Authors and Affiliations

  1. I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22/20 ul. S. Kovalevskoi, 620108, Yekaterinburg, Russian Federation

    A. Yu. Vigorov, I. A. Nizova, G. L. Levit, T. V. Matveeva, L. Sh. Sadretdinova & V. P. Krasnov

  2. Volgograd State Medical University of the Ministry of Health of the Russian Federation, 1 pl. Pavshikh Bortsov, 400131, Volgograd, Russian Federation

    O. I. Nazarov, N. S. Kovalev, D. A. Bakulin, D. V. Kurkin & I. N. Tyurenkov

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  1. A. Yu. Vigorov
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  2. I. A. Nizova
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  3. G. L. Levit
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  4. T. V. Matveeva
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  5. L. Sh. Sadretdinova
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  6. O. I. Nazarov
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  11. V. P. Krasnov
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Corresponding author

Correspondence to A. Yu. Vigorov.

Additional information

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2636–2644, December, 2022.

This work was financially supported by the Russian Foundation for Basic Research (Project No. 20-43-660045) and carried out within the framework of the Russian state assignment for the Postovsky Institute of Organic Synthesis of the Russian Academy of Sciences (Ural Branch) (IOS UB RAS) (Project No. AAAA-A19-119011790130-3).

The studies were carried out using the equipment of the Centre for Joint Use “Spectroscopy and Analysis of Organic Compounds” (CJU “SAOC”) at the IOS UB RAS.

All applicable international, national, and/or institutional guidelines for the care and use of animals have been followed. The animals were kept under standard conditions in accordance with Directive 2010/63/EU of the European Parliament and the Council of the European Union of September 22, 2010 on the protection of animals used for scientific purposes. The study plan was approved by the Regional Independent Ethics Committee at the Volgograd State Medical University of the Ministry of Health of the Russian Federation.

The authors declare no competing interests.

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Vigorov, A.Y., Nizova, I.A., Levit, G.L. et al. Synthesis and study of antiplatelet and antithrombotic activity of 4-substituted pyroglutamic acids. Russ Chem Bull 71, 2636–2644 (2022). https://doi.org/10.1007/s11172-022-3693-x

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  • DOI: https://doi.org/10.1007/s11172-022-3693-x

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