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A class of pyrimidine thioglycoside analogs ( 6a–h ) were synthesized from a reaction of 2-cyano-3,3-dimercapto- N -arylacrylamide ( 2a–d ) and thiourea to produce the corresponding 4-amino-2-mercapto- N -arylpyrimidine-5-carboxamide derivatives ( 3a–d ), and stirring of compounds ( 3a–d ) with peracylated α- d - gluco - and galacto-pyranosyl bromides ( 4a,b ) in DMF–sodium hydride gave the corresponding pyrimidine thioglycosides ( 5a–h ) . Deacetylation of the pyrimidine thioglycosides via a reaction with dry NH 3 /MeOH gave the corresponding free pyrimidine thioglycosides ( 6a–h ) . The compounds have been characterized by 13 C NMR, 1 H NMR, and IR. Pharmacological evaluation of compounds 3a–d , 5a–h , and 6a–h in vitro against SARS-COV-2 and Avian Influenza H5N1 virus strains revealed that some compounds possess interesting activity.

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The synthesis and antiviral screening of the first reported series of pyridine- and pyrimidine-based thioglycoside phosphoramidates are herein reported. They were prepared through two synthetic steps: The first step is via coupling of mercapto-derivatized heterocyclic bases with the appropriate α-bromo per-acetylated sugars. The second one is the hydrolysis of the acetate esters under basic conditions that were consequently conjugated with the phosphoramidating reagent to afford the desired thioglycoside protides. Eight compounds were evaluated for their antiviral activities against different viral cell lines, namely, adenovirus 7, HAV (hepatitis A) HM175, Coxsackievirus B4, and HSV-1 (herpes simplex virus type 1), in addition to the antiviral bioassay against ED-43/SG-Feo (VYG) replicon of HCV (hepatitis C virus) genotype 4a. Both compounds 5b and 11 showed notable antiviral activity against Coxsackie virus B4, reflected from the CC50 values of 17 and 20 μg/100 μL and IC50 values of 4.5 and 6.0 μg/100 μL, respectively. Same two compounds elicited remarkable activities toward herpes simplex virus type 1, represented by CC50 values of 17 and 16 μg/100 μL and IC50 values of 6.3 and 6.6 μg/100 μL, respectively. Combination of 11 with acyclovir elicited a notable synergistic activity in comparison with acyclovir alone, as inferred from herpes simplex polymerase enzyme inhibitory assay values of 2.64 and 4.78 μg/100 mL, respectively. Only compound 11 elicited a remarkable activity against HCV. Potential promising activities of compound 11 have been shown with respect to CC50, IC50, and enzyme assay inhibitory activities.

A first synthesis of a new class of novel cytosine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyrimidine-4-thiolate via condensation of N'-arylidene-2-cyanoacetohydrazides with sodium cyanocarbonimidodithioate salt, followed by coupling with halo sugars to give the corresponding cytosine thioglycoside analogs. Ammonolysis of the latter compounds afforded the free thioglycosides.