2. Academic Validation
  3. Azolo[5',1',2,3]pyrimido[5,4-e]tetrazolo[1,5-c]pyrimidines as dual-action antiglycators and α-glucosidase inhibitors

Azolo[5',1',2,3]pyrimido[5,4-e]tetrazolo[1,5-c]pyrimidines as dual-action antiglycators and α-glucosidase inhibitors

  • Bioorg Med Chem Lett. 2025 Dec 1:128:130333. doi: 10.1016/j.bmcl.2025.130333.
Grigoriy V Urakov 1,  Konstantin V Savateev 2,  Pavel A Slepukhin 3,  Vladimir L Rusinov 4,  Umida M Ibragimova 5,  Roman D Danilov 5,  Xenia I Zhukova 5,  Svetlana A Sorokina 5,  Violetta R Raiberg 5,  Roman A Litvinov 5,  Alexander A Spasov 5,  Denis A Babkov 5
Affiliations

Affiliations

  • 1 Ural Federal University named after the First President of Russia B.N. Eltsin, Mira St. 19, Yekaterinburg 620002, Russian Federation.
  • 2 Ural Federal University named after the First President of Russia B.N. Eltsin, Mira St. 19, Yekaterinburg 620002, Russian Federation. Electronic address: [email protected].
  • 3 Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Science, Sofii Kovalevskoy St. 22, Yekaterinburg 620137, Russian Federation.
  • 4 Ural Federal University named after the First President of Russia B.N. Eltsin, Mira St. 19, Yekaterinburg 620002, Russian Federation; Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Science, Sofii Kovalevskoy St. 22, Yekaterinburg 620137, Russian Federation.
  • 5 Volgograd State Medical University, Pavshikh Bortsov Sq. 1, Volgograd 400131, Russian Federation.
PMID: 40651538 DOI: 10.1016/j.bmcl.2025.130333
Abstract

The novel chemotype, azolo[5',1':2,3]pyrimido[5,4-e]tetrazolo[1,5-c]pyrimidines 12, with promising dual action antiglycating and α-glucosidase inhibiting activities was developed basen on reaction of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines 3 with (het)aroyl chlorides. The conditions for this process were optimized to achieve high yields of heterocycles 12 upon mild conditions whereas azido-tetrazole tautomerism was revealed for these products 12 and it was shown that the equilibrium is shifted towards azide tautomer. The obtained azolo[5',1':2,3]pyrimido[5,4-e]tetrazolo[1,5-c]pyrimidines 12 inhibited the glycation reaction in the BSA-glucose assay more strongly than pyridoxamine as a reference compound, which is promising in terms of preventing AGEs assosiated pathologies such as long-term complication of diabetes and Cancer. Furthermore, some heterocycles 12 inhibited α-glucosidase in the mid-micromolar range - more effectively than acarbose, with an IC50 17.52 μM for the lead compound 12k.

Keywords

Antiglycation; Azido-tetrazole tautomerism; Azolopyrimidines; Diabetes; Dual-action; α-Glucosidase.

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