Inhibition of the RNA-dependent RNA-polymerase from SARS-CoV-2 by 6-chloropurine isoxazoline-carbocyclic monophosphate nucleotides

Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a moderate activity of the nucleotides accompanied by cytotoxicity

Reactions of 1,2,4‐Oxadiazole[4,5‐a]piridinium Salts with Alcohols: the Synthesis of Alkoxybutadienyl 1,2,4‐Oxadiazoles

1,2,4-Oxadiazole[4,5-a]piridinium salts add alcohols and alkoxides to undergo electrocyclic ring opening affording alkoxybutadienyl 1,2,4-oxadiazole derivatives. The pyridinium salts represent a special class of Zincke salts that are prone to rearrange to give alkoxybutadienyl 1,2,4-oxadiazoles when treated with suitable nucleophiles or, alternatively, to give pyridones in the presence of bicarbonate. The pivotal tuning of the experimental conditions leads to a straightforward synthesis of valuable 1,2,4-oxadiazole derivatives. The mechanism is also discussed in the light of previous observations

Turn-folding in fluorescent anthracene-substituted cyclopenta[d]isoxazoline short peptides

Cyclopenta[d]isoxazoline aminols were used for the synthesis of b-turn mimics. The peptide chain choice ascertained the influence of their structural features on the applicability/reliability/robustness of these scaffolds as b-turn inducers and their limitations. The amino acid selection as well as steric demands can favor or disfavor the structure folding and the correct design of the peptide chains deeply influences the potential use of these nitrosocarbonyl-based compounds as turn-inducers