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

Vigorov, A. Yu.; Низова, И. А.; Левит, Г. Л.; Матвеева, Т. В.; Садретдинова, Л. Ш.; Nazarov, O. I.; Kovalev, N. S.; Бакулин, Д. А.; Куркин, Д. В.; Tyurenkov, I. N.; Краснов, В. П.

doi:10.1007/s11172-022-3693-x

Cited by 5 publications

(8 citation statements)

References 28 publications

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“…The assignment of signals in the NMR spectra was carried out via an analogy with [15,18,19] and was confirmed using the data of 2D experiments 1 H-1 H HSQC, HMBC, and 1 H-1 H NOESY for compounds 8a (Figures S31 and S32), 10a (Figures S43-S45), and 14 (Figures S55-S57).…”

Section: Chemistrymentioning

confidence: 76%

“…Figure 2. 4-Amino-5-oxoprolines as platelet aggregation inhibitors studied in previous works [15,16].…”

Section: Chemistrymentioning

confidence: 99%

“…(2S,4S)-4-Amino-1-phenyl-5-oxoproline (1a) [18] and (2S,4S)-4-amino-1-(4-fluorophenyl)-5-oxoproline (1b) [15] were chosen as the starting derivatives of 4-amino-5-oxoprolines (Scheme 1). During the first stage, the 4-amino group of 5-oxoprolines 1a,b was protected by introducing a tert-butoxycarbonyl (Boc) group through the action of Boc2O to afford acids 2a,b in high yields.…”

Section: Chemistrymentioning

confidence: 99%

“…(2S,4S)-4-Amino-1-phenyl-5-oxoproline (1a) [18] and (2S,4S)-4-amino-1-(4-fluorophenyl)-5-oxoproline (1b) [15] were chosen as the starting derivatives of 4-amino Starting from the previously described (2S,4S)-4-[(methyl)(phenyl)amino]-5-oxoproline (11) [19], we synthesized amides with piperidine (12) and morpholine (13) (Scheme 3). The coupling to the amino component (piperidine or morpholine) was carried out under the action of HBTU in DMF.…”

Section: Chemistrymentioning

confidence: 99%

“…We have previously shown that 4-amino-1-aryl-5-oxoprolines and 4-(arylamino oxoprolines exhibit antiplatelet and antithrombotic activity in vitro and in vivo (Figur the best results in this type of activity were shown by (2S,4S)-4-amino-1-(4-fluorophen 5-oxoproline [15,16]. Some derivatives of this series also demonstrated cerebroprotec and psychotropic activity in experiments in vivo [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Assessment of Antiplatelet and Antithrombotic Activity of 4-Amino-Substituted 5-Oxoproline Amides and Peptides

Krasnov,

Nizova,

Vigorov

et al. 2023

Molecules

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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.

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Section: Chemistrymentioning

confidence: 76%

“…Figure 2. 4-Amino-5-oxoprolines as platelet aggregation inhibitors studied in previous works [15,16].…”

Section: Chemistrymentioning

confidence: 99%