Fused azoloazines with antidiabetic activity

Русинов, В. Л.; Сапожникова, Ирина М.; Спасов, А. А.; Чупахин, О. Н.

doi:10.1007/s11172-022-3687-8

Cited by 13 publications

(3 citation statements)

References 101 publications

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“…It can be seen from Figure 1 and the cited literature sources that most of the known antidiabetic drugs in use include nitrogen heterocyclic moieties: azoles, azines, annelated azoloazines, oxazoles, thiazoles, and some others. The development of novel antidiabetic agents often involves the use of polynitrogen heterocyclic systems with more than two endocyclic heteroatoms (triazoles, tetrazoles, oxadiazoles, or their fused derivatives) as key scaffolds [8][9][10]. These moieties are very promising in drug design because they are often metabolically stable, easily participate in various intermolecular interactions through hydrogen bonding, conjugation, or van der Waals bonding with biological targets, and many of them are bioisosters of functional groups of endogenous molecules [11].…”

Section: Tetrazoles For Biomedicinementioning

confidence: 99%

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Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents

Trifonov,

Ostrovskii

2023

IJMS

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Tetrazole heterocycle is a promising scaffold in drug design, and it is incorporated into active pharmaceutical ingredients of medications of various actions: hypotensives, diuretics, antihistamines, antibiotics, analgesics, and others. This heterocyclic system is metabolically stable and easily participates in various intermolecular interactions with different biological targets through hydrogen bonding, conjugation, or van der Waals forces. In the present review, a systematic analysis of the activity of tetrazole derivatives against type 2 diabetes mellitus (T2DM) has been performed. As it was shown, the tetrazolyl moiety is a key fragment of many antidiabetic agents with different activities, including the following: peroxisome proliferator-activated receptors (PPARs) agonists, protein tyrosine phosphatase 1B (PTP1B) inhibitors, aldose reductase (AR) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, G protein-coupled receptor (GPCRs) agonists, glycogen phosphorylases (GP) Inhibitors, α-glycosidase (AG) Inhibitors, sodium glucose co-transporter (SGLT) inhibitors, fructose-1,6-bisphosphatase (FBPase) inhibitors, IkB kinase ε (IKKε) and TANK binding kinase 1 (TBK1) inhibitors, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In many cases, the tetrazole-containing leader compounds markedly exceed the activity of medications already known and used in T2DM therapy, and some of them are undergoing clinical trials. In addition, tetrazole derivatives are very often used to act on diabetes-related targets or to treat post-diabetic disorders.

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Section: Tetrazoles For Biomedicinementioning

confidence: 99%

“…More effective compounds are now being developed. It can be noted that practically all such compounds contain polynitrogen heterocyclic moieties [9]. Given this, one would expect that tetrazoles would also be in demand in this context, but there are few such publications.…”

Section: Dipeptidyl Peptidase-4 (Dpp-4) Inhibitors and Glucagon-like ...mentioning

confidence: 99%

Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents

Trifonov,

Ostrovskii

2023

IJMS

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“…In particular, they exhibit antiviral activity, and some compounds of this series are characterized by activity against the main 3CLpro-2 protease of the coronavirus, which is involved in the maturation and replication of the SARS-CoV-2 virus [7]. In addition, azoloazines have demonstrated a pronounced protective effect against septic shock and exhibit antibacterial, antidiabetic, and anticoagulant activities [8][9][10]. It is worth mentioning that substituted 1,2,4-triazolo[1,5-a]pyrimidin-7-ones have a higher anticoagulant activity than that of the wellknown drug dabigatran etexilate, which also contains azole and azine moieties [2].…”

Section: Introductionmentioning

confidence: 99%

Novel Substituted Azoloazines with Anticoagulant Activity

Spasov,

Fedorova,

Rasputin

et al. 2023

IJMS

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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.

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