Investigation of 8-Aza-7-Deaza Purine Nucleoside Derivatives

Abstract

Glycosylation of 6-amino-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine and its iodo- and bromo- analogues with the protected ribofuranose and 2′-deoxyribofuranose under different conditions resulted in the synthesis of N9- and N8-glycosylated purine nucleosides. Five key intermediate nucleosides, having 6-methoxy, 7-iodo, and 2-bromo groups, were further derivatized to 23 final 8-aza-7-deazapurine nucleoside derivatives. The structures of N9- and N8-glycosylated products were assigned based on UV and NMR spectra. HMBC analysis of 2D NMR spectra and X-ray crystallographic studies of the representative compounds unambiguously verified the connection of ribose ring to N9- or N8-position of the purine ring. The anticancer activity of these new compounds was evaluated.

Novel Pyrazolo[3,4-d]pyrimidin-4-one Derivatives as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation

“…9 To our knowledge, the natural purine nucleoside heterocyclic base 10 is widely distributed in organisms as the raw material for the production of ATP, 11 vidarabine, 12 coenzyme A, 13 and other biologically essential biomolecules and is clinically used in treatments of various human diseases. 14 Pyrazolo [3,4-d]pyrimidin-4(5H)-one scaffolds, as bioisosteres 15 of the natural purine nucleoside heterocyclic base such as guanosine and guanine deoxyribonucleoside 16 (Figure 2), have drawn considerable attention as they are involved in various pharmacologically active compounds, including antiinflammatory, 17 antibacterial, 18 anticancer, 19 antiproliferative, 20 anti-Alzheimer's, 21 antierectile dysfunction, 22 antifungal, 23 CNS-modulating, 24 and antiviral compounds, 25 and treat insomnia 26 activities (Figure 1). Therefore, pyrazolo [3,4-d]pyrimidin-4(5H)-one scaffolds have special structural functionalities and excellent biological characteristics and are regarded as a potential drug candidate against agricultural pathogens.…”