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

Abstract

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.

Graphical Abstract

Keywords:

• Pyrimidine thioglycosides
• favipiravir (Avigan) analogs
• antibird flu influenza
• anti-influenza A virus (subtype H5N1)
• avian influenza

Acknowledgment

We would like to thank Prof. Dr. Mohamed Ahmed Ali, Director of Center of Scientific Excellence for Influenza Viruses (CSEIV), National Research Centre, for performing biological assay tests.

Conflict of interest

The authors confirm that this article content has no conflict of interest.