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  • Title: 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.
    Author: Rusinov VL, Sapozhnikova IM, Bliznik AM, Chupakhin ON, Charushin VN, Spasov AA, Vassiliev PM, Kuznetsova VA, Rashchenko AI, Babkov DA.
    Journal: Arch Pharm (Weinheim); 2017 May; 350(5):. PubMed ID: 28393419.
    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.
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