Recent Trend in the Chemistry of Triazolopyrimidines and their Applications

Abstract

This review deals with the synthetic methods, chemical reactions, and applications of triazolopyrimidine derivatives. The synthetic methods and chemical reactions are subdivided into groups according to the junction between triazole and pyrimidine moieties for instance [1,2,4]triazolo[1,5-a]pyrimidine, [1,2,4]triazolo[1,5-c]pyrimidine, [1,2,3]triazolo[1,5-a]pyrimidine, [1,2,3]triazolo[1,5-c]pyrimidine, [1,2,4]triazolo[4,3-c]pyrimidine, and [1,2,4]triazolo[4,3-a]pyrimidine. Pharmacological activity of triazolopyrimidins is also reported.

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

“…Triazolopyrimidine represents a privileged structure in agrochemical and medicinal chemistry, with numerous derivatives that have found applications in several biological and medical fields. [1][2][3] Among the eight different triazolopyrimidine isomers existing in nature, [1,2,4]triazolo [1,5-a]pyrimidine (hereafter abbreviated TZP for convenience) has been the most studied and used isomer in medicinal chemistry, especially to design and synthesize novel anti-infective agents. [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.…”

“…MCRs represent a powerful approach for achieving diversity and complexity of organic compounds, reducing the number of reaction steps and the environmental impact, thus combining molecular diversity, depending on the structures of the reagents, the solvent, and the catalyst, with eco-compatibility. Some examples of Biginelli-like reactions for the synthesis of the TZP scaffold that combine aldehydes, compounds with an active methylene group, and polyfunctional aminotriazoles have been reported in the literature (readers are directed to reviews), 3,[12][13][14][15][16] mainly furnishing C-2 unsubstituted TZP derivatives, such as 4,5,6,7-tetrahydro-TZPs, 17 4,7-dihydro-TZPs, 18,19 and aromatic TZP analogues 20 (Fig. 1 general structures I-IV).…”

“…3–5 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…”

“…Some examples of Biginelli-like reactions for the synthesis of the TZP scaffold that combine aldehydes, compounds with an active methylene group, and polyfunctional aminotriazoles have been reported in the literature (readers are directed to reviews), 3,12–16 mainly furnishing C-2 unsubstituted TZP derivatives, such as 4,5,6,7-tetrahydro-TZPs, 17 4,7-dihydro-TZPs, 18,19 and aromatic TZP analogues 20 (Fig. 1 – general structures I–IV).…”

“…[1][2][3] Among the eight different triazolopyrimidine isomers existing in nature, [1,2,4]triazolo [1,5-a]pyrimidine (hereafter abbreviated TZP for convenience) has been the most studied and used isomer in medicinal chemistry, especially to design and synthesize novel anti-infective agents. [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.…”