Synthesis and antiviral activity of nucleoside analogs based on 1,2,4-triazolo[3,2-c][1,2,4]triazin-7-ones

Abstract

Nucleoside analogs containing hydroxybutyl, hydroxyethoxymethyl, allyloxymethyl, and propargyloxymethyl fragments were synthesized based on 1,2,4 triazolo[3,2 c][1,2,4]triazin 7 ones isosteric to purine bases. Some of the compounds obtained inhibit in vitro reproduction of influenza and respiratory syncytial virus infection.

Bicyclic 5-6 Systems With One Bridgehead (Ring Junction) Nitrogen Atom: Four Extra Heteroatoms 2:2

“…19.5.1.1(ii) [1,2,4]triazolo [1,5-a][1,3,5]triazines Despite five resonance structures of the anion 61, the N-alkylation of [1,2,4] [25][26] The fusion of 69 with an excess of (2-acetoxyethoxy)methyl acetate 73 at 150 °C in the presence of ZnCl2 afforded regioselectively the corresponding 1-(2-acetoxyethoxy)methyl derivatives 74. [27][28] Two methods were developed for the N-glycosylation of 69: treatment of 69 with N,O-bis-(trimethylsilyl)acetamide and trimethylsilyl triflate followed by addition of -D-glucose pentaacetate 75 (method A) or reaction of the sodium salts of 69 with tetra-acetyl--D-bromoglucose 76 in DMF under heating (method B). In both cases, the N-glycosylations took place at the N1 position affording nucleosides 77 with -configurations.…”

Triazavirin—A Novel Effective Antiviral Drug

“…The reaction of Triazavirin with bromobutyl acetate leads to the formation of the only N4-isomer [ 41 ], which can be regarded as a structural analogue of acyclic nucleosides ( Scheme 11 ).…”

“…Additionally, the reversibility of the reaction and the intermolecular mechanism of the process were substantiated by studies with isotope labels. A series of non-natural nucleoside analogues have been obtained by exploiting the regiospecific reaction of NH-Triazavirin with alkylating agents on heating under neat conditions ( Scheme 16 ) [ 41 ].…”

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

“…However, 103-105 showed remarkable activity against influenza A virus, particularly the H3 N2 strain. [100] A set of 1,2,4-triazolo[5,1-c][1,2,4]triazin-7-ones bearing substituents at 4 positions of the heterocycle that mimic the nucleoside's glycoside moiety (106)(107)(108)(109)(110)(111) was synthesized, and their antiviral activity against herpes simplex virus 1 (HSV-1) was assessed (Figure 35). Compounds with 2-hydroxy-ethoxymethyl functionality 106-108 inhibited the virus replication by 50 percent at concentrations higher than 250 μM.…”

“…Compounds 100 – 102 exhibited anti‐influenza A activity that was almost equivalent to, or even better than, the activity of rimantadine as well as anti‐influenza B activity shown to be comparable to rimantadine. However, 103 – 105 showed remarkable activity against influenza A virus, particularly the H3 N2 strain …”