Novel 8-arylidenetetrahydroquinazoline N-oxides: synthesis, photophysical properties and biological evaluation

Sedenkova, Kseniya N.; Vasilenko, Dmitry A.; Zverev, Denis V.; Sadovnikov, Kirill S.; Gracheva, Yulia A.; Grishin, Yu. K.; Kuznetsova, Т. S.; Милаева, Е. Р.; Averina, Elena B.

doi:10.1016/j.mencom.2021.01.011

Cited by 2 publications

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As excellent substrates for the aromatic nucleophilic substitution, 4-halogenopyrimidine N-oxides could be transformed into pyrimidine N-oxides bearing amino, azido, cyano, hydroxy, alkoxy, and phenoxy groups in position 4. [12,13,15,[29][30][31] Another direction of functionalization of tetrahydroquinazoline N-oxides was Knoevenagel-type condensation employing methyl group in position 2, which afforded fluorescent compounds of type 7 (Figure 2). [16,31] Altogether, it makes tetrahydroquinazoline N-oxides attractive starting compounds for the synthesis of biologically active derivatives, as demonstrated by the elaboration of novel chemotypes of TBEV reproduction inhibitors [12][13][14] and AMPA receptor positive and negative modulators [32,33] with tetrahydroquinazoline core.…”

Section: Series Designmentioning

confidence: 99%

Tetrahydroquinazoline N‐oxide derivatives inhibit reproduction of tick‐borne and mosquito‐borne flaviviruses

Sedenkova

Uvarova

Назарова

et al. 2023

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

Tick‐borne encephalitis virus (TBEV), yellow fever virus (YFV), and West Nile virus (WNV) are flaviviruses causing emerging arthropod‐borne infections of a great public health concern. Clinically approved drugs are not available to complement or replace the existing vaccines, which do not provide sufficient coverage. Thus, the discovery and characterization of new antiflaviviral chemotypes would advance studies in this field. In this study, a series of tetrahydroquinazoline N‐oxides was synthesized, and the antiviral activity of the compounds was assessed against TBEV, YFV, and WNV using the plaque reduction assay along with the cytotoxicity to the corresponding cell lines (porcine embryo kidney and Vero). Most of the studied compounds were active against TBEV (EC50 2 to 33 μM) and WNV (EC50 0.15 to 34 μM) and a few also demonstrated inhibitory activity against YFV (EC50 0.18 to 41 μM). To investigate the potential mechanism of action of the synthesized compounds, time‐of‐addition (TOA) experiments and virus yield reduction assays were performed for TBEV. The TOA studies suggested that the antiviral activity of the compounds should affect the early stages of the viral replication cycle after cell entry. Compounds with tetrahydroquinazoline N‐oxide scaffold show a broad spectrum of activity against flaviviruses and represent a promising chemotype for antiviral drug discovery.

show abstract