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.
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.
authors.affiliation: Ural Federal University named after the First President of Russia B.N. Yeltsin, Ekaterinburg, Russia.
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Rusinov
authors.affiliation: Ural Federal University named after the First President of Russia B.N. Yeltsin, Ekaterinburg, Russia.
authors.forename: Irina M
authors.identifier: http://orcid.org/0000-0002-5193-9670
authors.initials: IM
authors.lastname: Sapozhnikova
authors.affiliation: Ural Federal University named after the First President of Russia B.N. Yeltsin, Ekaterinburg, Russia.
authors.forename: Anastasiya M
authors.initials: AM
authors.lastname: Bliznik
authors.affiliation: Ural Federal University named after the First President of Russia B.N. Yeltsin, Ekaterinburg, Russia.
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Chupakhin
authors.affiliation: Ural Federal University named after the First President of Russia B.N. Yeltsin, Ekaterinburg, Russia.
authors.forename: Valery N
authors.initials: VN
authors.lastname: Charushin
authors.affiliation: Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Spasov
authors.affiliation: Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia.
authors.forename: Pavel M
authors.initials: PM
authors.lastname: Vassiliev
authors.affiliation: Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Kuznetsova
authors.affiliation: Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia.
authors.forename: Andrey I
authors.initials: AI
authors.lastname: Rashchenko
authors.affiliation: Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Babkov
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D014227:Triazines; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Antiglycation; Azolotriazines; Cross-link breakers; Diabetes mellitus; Dipeptidyl peptidase-4 inhibitors