Synthesis and Evaluation of Novel [1,2,4]Triazolo[5,1‐c][1,2,4]‐triazines and Pyrazolo[5,1‐c][1,2,4]triazines as Potential Antidiabetic Agents

Abstract

Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers. From the two considered classes of heterocyclic compounds, the pyrazolotriazines showed the highest potency as antiglycating agents and DPP4 inhibitors. Structure-activity relationships (SAR) for these compounds, which can be considered as potential drugs for the treatment of type 2 diabetes, were evaluated.

6‐Nitroazolo[1,5‐a]pyrimidin‐7(4H)‐ones as Antidiabetic Agents

“…We have previously reported that substituted [1,2,4]triazolo[5,1‐ c ][1,2,4]triazine‐4(1 H )‐ones and pyrazolo[5,1‐ c ][1,2,4]triazine‐4(1 H )‐ones have the activity superior to aminoguanidine against the formation of AGEs induced by glucose or methylglyoxal . In addition, several micromolar inhibitors of dipeptidyl peptidase 4 have been identified in this series.…”

Synthetic approaches to 1,2,4-triazolo[5,1-c][1,2,4]triazin-7-ones as basic heterocyclic structures of the antiviral drug Riamilovir (“Triazavirin®”) active against SARS-CoV-2 (COVID-19)

“…Thus, the reaction of 5-diazo-1,2,4-triazoles 19, prepared by treating 5-amino-1,2,4-triazoles 20 with nitrous acid, with malonic ester resulted in 1,2,4-triazolylhydrazones 21, and their cyclization under basic conditions led to the formation of salts of 6-ethoxycarbonyl-1,2,4-triazolo[5,1-c]-1,2,4-triazin-7 (4H)-ones 22. [26][27][28]31,32 A number of derivatives of compound 22 were evaluated for a broad range of antidiabetic activities. The majority of these compounds have demonstrated a potent inhibitory activity against glucose-induced and methylglyoxalinduced glycation.…”

In vitrocytotoxicity and antibacterial activity of [Pd(AMTTO)(PPh3)2]: a novel promising palladium(ii) complex

“…39 From a biochemistry perspective, 1,2,4-triazine derivatives and their metal complexes have attracted considerable attention due to their widespread biological significance and pharmacological applications. Several reports in the literature deal with their applications as anticancer, [40][41][42][43][44][45][46][47][48] antimicrobial, 49,50 antiinflammatory, 51,52 anti-HIV, 53,54 antimalarial, 55 antidiabetic, 56 anticonvulsant, 57 and antiviral drugs. 58 In general, their biological activities may be attributed to the presence of a toxophoric 4NCS group as well as the CQN linkage and the strong aromaticity in the 1,2,4-triazine ring systems.…”