Benzimidazoazapurines: Design, Synthesis, and Photophysical Study

Fedotov, Victor V.; Ulomsky, E. N.; Belskaya, Nataliya P.; Eltyshev, Alexander K.; Саватеев, Константин В.; Воинков, Е. К.; Lyapustin, Daniil N.; Русинов, В. Л.

doi:10.1021/acs.joc.1c00760

Cited by 15 publications

(7 citation statements)

References 47 publications

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“…The monitoring of the reaction progress was performed by using TLC on Sorbfil plates (Imid LTD, Russia, Krasnodar) eluent is CHCl 3 . Heterocycles 3b, 3d, 3e, 7, 10a, 10b were synthesized in accordance with literature data: 3b [ 17 ] , 3d, 3e [ 18 ] , 7 [ 19 ] , 10a, 10b [ 20 ] . All synthesized compounds are >95% pure by elemental analysis.…”

Section: Methodsmentioning

confidence: 99%

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Azolo[1,5-a]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

et al. 2022

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Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

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Section: Methodsmentioning

confidence: 99%

“…2021/056, 15 June 2021. All sections of this study adhere to the ARRIVE Guidelines for reporting animal research [ 20 ].…”

mentioning

confidence: 99%

Azolo[1,5-a]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

et al. 2022

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“…The monitoring of the reaction progress was performed by using TLC on Silufol UV254 plates (eluent is CHCl3). Heterocycles 3b, 3d, 3e, 7, 10a, 10b were synthesized in accordance with literature data: 3b [16], 3d, 3e [17], 7 [18], 10a, 10b [19]. All synthesized compounds are >95% pure by elemental analysis.…”

Section: Chemistrymentioning

confidence: 99%

Azolo[1,5-a]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

Саватеев¹,

Fedotov²,

Русинов³

et al. 2021

Preprint

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Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

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“…V. Fedotov and co-workers in 2021. 57 (Scheme 21) They screened various copper catalysts and it was observed that Cu(OAc) 2 ·H 2 O (1.0 equivalent) was the most effective catalyst. The yield of the desired product was improved (84%) by increasing the amount of the catalyst, Cu(OAc) 2 ·H 2 O (2.5 equivalent) at 100 °C.…”

Section: Transition Metal and Nhc Catalyzed Synthesismentioning

confidence: 99%

“…45,46 Several other methods have also been developed which are catalyzed by a variety of metals such as Palladium, [47][48][49] rhodium, 50,51 and Copper. [52][53][54][55][56][57] Greener alternatives have also been developed such as those being mediated by Iodine. [58][59][60][61] or synthesis being performed in the aqueous medium.…”

Section: Introductionmentioning

confidence: 99%