Insights into the recent progress in the medicinal chemistry of pyranopyrimidine analogs

Abstract

Heterocycles containing the pyranopyrimidine motif have attracted the interest of researchers in recent decades due to their ability to synthesize and explore at a large scale to explore the biological diversity. Therefore, this review highlights the biological characteristics and synthetic approaches adopted to prepare pyranopyrimidine analogs in the last five years. Several novel preparation procedures have been summarized to synthesize these compounds using ionic, basic, or nanocatalysts or catalyst-free conditions to obtain these compounds in good yields. Pyranopyrimidines could also be used as ligands in the preparation of metal complexes with increased biological potency. The different sections include the antimicrobial, antitubercular, antimalarial, antiviral "SARS-CoV-2 inhibitors", antidiabetic, antitumor, cytotoxic, antiinflammatory, antioxidant, anticoagulant, urease inhibitory activities, and tyrosine inhibitors. The results are discussed based on the structure-activity relationships (SARs) and the mechanism of action.

Fig. 1. The conceivable structural isomers of pyranopyrimidines.

Fig. 2. Patterns of compounds with pyranopyrimidine motif with privileged biologically active characters.

Scheme 1. Synthesis and antibacterial results of tetrahydro-2H-pyranopyrimidines.

Scheme 2. Synthesis of bicyclic pyranopyrimidines.

Scheme 3. Synthesis of methyl tetrahydropyranopyrimidine-carboxylates.

Scheme 4. Synthesis, antibacterial results, and SARs of pyranopyrimidines.

Scheme 5. Synthesis and SARs of bicyclic pyranopyrimidines.

Scheme 6. Synthesis of triazole-based pyranopyrimidine series.

Scheme 7. Synthesis of tricyclic pyranopyrimidines.

Scheme 8. Synthesis of bicyclic pyranopyrimidines.

Scheme 9. Synthesis of tri- and polycyclic pyranopyrimidines.

Scheme 10. Synthetic routes for the multi-step synthesis of pyranodipyrimidine-diones.

Scheme 11. Synthesis of pyrazolo-pyranopyrimidine-diones.

Scheme 12. Synthetic routes for the preparation of polycyclic benzochromenopyrimidines.

Fig. 3. Synthesis and SARs of tetrahydropyranopyrimidinones as antibacterial agents.

Scheme 13. Synthesis and SARs of bioactive hexahydropyranopyrimidines.

Scheme 14. Multicomponent synthesis and SARs of pyranopyrimidines.

Scheme 15. Synthesis of bicyclic pyranopyrimidine derivatives.

Scheme 16. Synthesis of Mn(ii)-L1 and Mn(ii)-L2 complexes.

Scheme 17. The SARs and synthesis of Mn(ii) complexes of pyranodipyrimidine as antimicrobial agents.

Scheme 18. Synthesis of binary pyrazoles-based bicyclic pyranopyrimidines.

Scheme 19. Synthesis of chromenopyrano[1,2,4]triazolopyrimidines, and chromenopyranopyrimidinones.

Scheme 20. Synthesis of chromenopyrimidines.

Scheme 21. Synthesis of tetrahydropyranopyrimidines and their ethyl formimidate derivatives.

Scheme 22. Synthesis of pyranopyrano[2,3-d]pyrimidinones and chromenopyrano[2,3-d]pyrimidinones.

Scheme 23. The synthetic route of pyranopyrimidines under catalytic conditions.

Scheme 24. Multi-step synthesis of 5H-chromenopyrimidinol derivatives.

Scheme 25. Multicomponent synthesis and SARs of polycyclic diazanaphtho-tetraphene-diones.

Scheme 26. Synthesis of binary and tricyclic pyranopyrimidines.

Scheme 27. Synthesis and SARs of chromenopyrano[2,3-d]pyrimidine-diones as antiHIV-1 and HIV-2.

Fig. 4. The structure of pyranodipyrimidine-4,6-diol as an antiviral agent.

Scheme 28. Synthesis of tetrahydro-pyranopyrimidines.

Fig. 5. SARs of pyranopyrimidinones as α-amylase and α-glucosidase inhibitors.

Scheme 29. Synthesis of chromenopyranopyrimidine-triones.

Scheme 30. Synthesis of dihydropyrano[2,3-d]pyrimidine-diones.

Scheme 31. Synthesis of pyranopyrimidines and their S-alkyl analogs.

Scheme 32. Synthesis and SARs of 5-amino-6-cyano-pyranopyrimidines.

Scheme 33. Multi-step synthesis of ethyl-1,2,3-triazolyl-pyrano-pyrimidine-carboxylates.

Scheme 34. The reactivity of enaminonitrile toward the variety of reagents for the synthesis of pyranopyrimidine heterocycles.

Scheme 35. Synthesis of polycyclic heterocycles with pyranopyrimidines.

Scheme 36. Synthesis of 12H-spiro[indoloquinazoline-pyranopyrimidine] derivatives.

Scheme 37. Synthesis of bicyclic pyranopyrimidines.

Scheme 38. Synthesis of dihydropyranopyrimidine-triones.

Scheme 39. Multicomponent synthesis of 2H-chromenopyrimidine-diones.

Scheme 40. Synthesis of polycyclic pyranopyrimidines.

Scheme 41. Synthesis of benzochromenopyrimidinones.

Fig. 6. SARs of tetrahydropyranopyrimidinones.

Scheme 42. Schematic synthesis of substituted bicyclic pyranopyrimidines and tricyclic pyranodipyrimidines.

Fig. 7. The structures of the tricyclic pyrazolopyrano-pyrimidine-diones as antioxidizing agents.

Fig. 8. The structures of 5H-chromenopyrimidinol derivatives as antioxidant agents.

Scheme 43. Multi-step synthesis of pyrazolopyranopyrimidinyl-chromenone and SARs of these compounds as potential antioxidant agents.

Scheme 44. Synthesis of pyranopyrimidine-based carbohydrates.

Scheme 45. Synthesis of chromenopyrimidinones and chromeno[1,2,4]triazolopyrimidinones.

Fig. 9. The SARs of polycyclic pyranopyrimidines as efficient antityrosinase agents.

Scheme 46. Schematic routes for the multi-step synthesis of pyranopyrimidines bearing triazole ring.

Scheme 47. Multicomponent synthesis and SARs of bicyclic pyranopyrimidines as urease inhibitors.

Khaled M. Elattar

Ayman Y. El-Khateeb

Sahar E. Hamed