Triazolopyrimidine Derivatives: An Updated Review on Recent Advances in Synthesis, Biological Activities and Drug Delivery Aspects

Abstract

Molecules containing triazolopyrimidine core showed diverse biological activities, including anti-Alzheimer, antidiabetes, anticancer, antimicrobial, antituberculosis, antiviral, antimalarial, anti-inflammatory, anti-parkinsonism activities, and treatment of glaucoma. Triazolopyrimidines have around 8 isomeric structures including the most stable 1,2,4-triazolo[1,5-a] pyrimidine ones. Triazolopyrimidines were obtained by using various chemical reactions, among them a) 1,2,4-triazole nucleus annulation to pyrimidine, b) pyrimidines annulation to 1,2,4-triazole structure, c) 1,2,4-triazolo[l,5-a] pyrimidines rearrangement, and d) pyrimido-tetrazine rearrangement. This review discusses synthetic methods, recent pharmacological actions and drug delivery perspectives of triazolopyrimidines.

Switching the three-component Biginelli-like reaction conditions for the regioselective synthesis of new 2-amino[1,2,4]triazolo[1,5-a]pyrimidines

“…[3][4][5] However, recent articles and reviews show the potential of this nucleus to develop compounds endowed with several biological activities, also taking advantage of its favourable pharmacokinetic properties. 1,3,4,6 For some years, our group has been involved in the synthesis of TZP-based compounds as inhibitors of RNA viruses, mainly as an anti-influenza virus (IV) agents able to inhibit RNA-dependent RNA polymerase (RdRP) PA-PB1 subunits interaction. [7][8][9][10] Starting from the hit compound 1 (Scheme 1a), several compounds were designed and synthesized by exploring the role of the C-2 amide substituent and modifying the TZP nucleus by: (i) aromatization of the 4,7-dihydro- [1,2,4]triazolo [1,5-a]pyrimidine core, (ii) exchange of 5-methyl and 7-phenyl moieties, (iii) inversion of the C-2 amide link, (iv) decoration of the C-5/C-7 phenyl ring with different substituents, (v) removal of the methyl moiety while maintaining only a phenyl ring at the C-7, C-5, or C-6 position, and (vi) replacement of the C-7 methyl group by a hydroxyl group (Scheme 1a).…”