Anti-Covid-19 Drug Analogues: Synthesis of Novel Pyrimidine Thioglycosides as Antiviral Agents Against SARS-COV-2 and Avian Influenza H5N1 Viruses.

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 NH3/MeOH gave the corresponding free pyrimidine thioglycosides (6a-h). The compounds have been characterized by 13C NMR, 1H 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.

Synthesis of novel pyrimidine thioglycosides as structural analogs of favipiravir (avigan) and their antibird flu virus activity.

Novel class of amino pyrimidine thioglycoside derivatives were designed from sodium 2-cyano-3-(arylamino)prop-1-ene-1,1-bis(thiolate) 1a-d and guanidine hydrochloride 2 to afford the corresponding sodium 2,6-diamino-5-aryl-1,2-dihydropyrimidine-4-thiolate 3a-d, which in coupling with peracylated α-D-gluco- and galactopyranosyl bromides 5a,b in DMF gave the corresponding pyrimidine thioglycosides 6a-h. Acidification of 2,6-diamino-5-aryl-1,2-dihydropyrimidine-4-thiolate salts 3a-d with hydrochloric acid formed the corresponding pyrimidine-4-thioles 4a-d. The latter were stirred with peracetylated halo sugars α-D-gluco- and galacto-pyranosyl bromides in sodium hydride and DMF to yield the pyrimidine thioglycosides 6a-h. Deacetylation of the pyrimidine thioglycosides gave the corresponding free pyrimidine thioglycosides 7a-h. The compounds were characterized by 13C NMR, 1H NMR, and IR. The pyrimidine thioglycosides 6a-h and free pyrimidine thioglycosides 7a-h were tested against H5N1 virus strain and exhibited high to moderate activity.

Toward Developing Therapies against Corona Virus: Synthesis and Anti-Avian Influenza Virus Activity of Novel Cytosine Thioglycoside Analogues.

A series of pyrimidine and pyrimidine thioglycoside derivatives were newly synthesized using sodium 2-cyano-3-(arylamino)prop-1-ene-1,1-bis(thiolates) and urea to give the corresponding sodium 6-amino-5-aryl-2-oxo-1,2-dihydropyrimidine-4-thiolates. Stirring of the latter with peracetylated α-d-gluco- and galacto-pyranosyl bromides in DMF afforded the corresponding pyrimidine thioglycosides. On the other hand, treatment of 6-amino-5-aryl-2-oxo-1,2-dihydropyrimidine-4-thiolate salts with hydrochloric acid produced the corresponding pyrimidine-4-thioles, which on stirring with α-d-gluco- and galacto-pyranosyl bromides in sodium hydride and DMF gave the corresponding pyrimidine thioglycosides. Deacetylation of the protected pyrimidine thioglycosides gave the corresponding free pyrimidine thioglycosides. The synthesized compounds have been characterized by 13C NMR, 1H NMR, and IR spectroscopy. The pyrimidine thioglycosides and free pyrimidine thioglycosides were tested against avian influenza H5N1 virus strain and exhibited highest to moderate activity.