Synthesis and Assessment of Antiplatelet and Antithrombotic Activity of 4-Amino-Substituted 5-Oxoproline Amides and Peptides
Victor P. Krasnov,
Irina A. Nizova,
Alexey Yu. Vigorov,
Tatyana V. Matveeva,
Galina L. Levit,
Mikhail I. Kodess,
Marina A. Ezhikova,
Pavel A. Slepukhin,
Dmitry A. Bakulin,
Ivan N. Tyurenkov,
Valery N. Charushin
Affiliations
Victor P. Krasnov
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Irina A. Nizova
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Alexey Yu. Vigorov
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Tatyana V. Matveeva
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Galina L. Levit
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Mikhail I. Kodess
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Marina A. Ezhikova
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Pavel A. Slepukhin
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
Dmitry A. Bakulin
Laboratory of Pharmacology of Cardiovascular Agents, Scientific Center for Innovative Medicines, Volgograd State Medical University, Volgograd 400131, Russia
Ivan N. Tyurenkov
Laboratory of Pharmacology of Cardiovascular Agents, Scientific Center for Innovative Medicines, Volgograd State Medical University, Volgograd 400131, Russia
Valery N. Charushin
Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, Russia
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. It has been found that the newly obtained compounds slow down the process of thrombus formation in a model of arterial and venous thrombosis, without affecting plasma hemostasis parameters. (2S,4S)-4-Amino-1-(4-fluorophenyl)-5-oxoprolyl-(S)-phenylalanine proved to be the most efficient among the studied derivatives. The results obtained indicate the advisability of further studies on 5-oxoproline derivatives in order to design pharmaceutical agents for the prevention and treatment of the consequences of thrombosis.