Nucleophilic substitution of nitro group in nitrotriazolotriazines as a model of potential interaction with cysteine-containing proteins

Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents

“…However, none of the synthesized compounds exhibited activity against HIV-2. [85] Frączek et al synthesized two classes based on the 3,4disubstituted-4,5-dihydro-1H-1,2,4-triazole-5-thione scaffold, either attached via amide linker (88,89), or methylene spacer (90,91) and their antiviral potency toward HIV was investigated ( Figure 30 inhibitors (NNRTIs). Both compounds exhibited potent inhibitory activity and adequate aqueous solubility in comparison with the standard nevapirine (NVP) drug, which could, therefore, serve as a lead scaffold for the production of new watersoluble salts of 1,2,4-triazole NNRTIs.…”

“…The insertion of Schiff base pharmacophore at nitrogen atom in 1,2,4-triazole ring strengthened the inhibitory action against HSV-1. [88] The SARs studies of 3,4,5-trisubstituted-1,2,4-triazoles in series I (87)(88)(89) and series II (90)(91)(92)(93)(94)(95)(96)(97)(98) have demonstrated that NNRTIs in series I vary in the substitution of aryl rings in which less positive moieties are preferred in the vicinity of both orthoand para-position of the phenyl ring (R 3 ). As well, the presence of no or small substitute fragments in the 5-position of the triazole core (R 1 ) appears to be particularly favourable routes to increase the potency, and any larger group tends to decrease the inhibitory action.…”

“…Triazavirin (TZV, 99) is a guanine nucleotide analog with a novel triazolotriazine core (Figure 33) that represents a novel structural class of non-nucleoside antiviral drugs. [90] TZV is a broad-spectrum antiviral drug originally developed in Russia through a joint effort of Ural Federal University, Ural Center for Biopharma Technologies, Russian Academy of Sciences, and Medsintez Pharmaceutical that has been shown to be effective against influenza A and B, including the H5 N1 strain. [91] Triazavirin testing against SARS-CoV-2 began in February 2020 [92] due to the similarities between H5 N1 and SARS-CoV-2, the coronavirus responsible for COVID-19.…”

“…1,2,4‐Triazole annelated di‐ and triazines scaffolds are of substantial interest due to their diverse biological activities, including antiviral activity, and are incorporated into some commercially available drugs. Triazavirin (TZV, 99 ) is a guanine nucleotide analog with a novel triazolotriazine core (Figure ) that represents a novel structural class of non‐nucleoside antiviral drugs . TZV is a broad‐spectrum antiviral drug originally developed in Russia through a joint effort of Ural Federal University, Ural Center for Biopharma Technologies, Russian Academy of Sciences, and Medsintez Pharmaceutical that has been shown to be effective against influenza A and B, including the H5 N1 strain .…”

Current and Future Direct-Acting Antivirals Against COVID-19

“…Triazavirin is a broad-spectrum purine nucleoside base analog developed by the Russians to treat flu patients ( Karpenko et al, 2010 ; Rusinov et al, 2015 ). A small clinical trial indicates that Triazavirin has a small, insignificant benefit over placebo control in treating COVID-19 patients ( Wu et al, 2020a ).…”