1,2,4-Triazole nucleosides

Abstract

As antiviral agents and intermediates therefor, 3-substituted 1-(β-D-glycosyl)-1,2,4-triazoles, O-acylated analogs thereof, and 5'- and 3',5'-cyclic phosphates of the triazole nucleosides, "glycosyl" being .[.a pentofuranosyl moiety, preferably one whose 2'-oxygen is trans to the triazole aglycon, e.g., xylofuranosyl,.]. ribofuranosyl, .[.2-0-methylribofuranosyl, etc.,.]. the triazole aglycon being 3-substituted with cyano, methylcarboxylate, carboxamidoxime, carboxamido-, thiocarboxamido, or carboxamidine. Preparation of these nucleosides is by silylation of the substituted triazole followed by glycosylation with the appropriate blocked glycosyl halide. Alternatively, acid-catalyzed fusion of the requisite 1,2,4-triazole with an O-acylated pentofuranose yields the nucleosides.

We claim: 
     
       1. A compound of structure ##STR8## wherein G is .[.a pentofuranosyl moiety whose 2'-oxygen is trans to the aglycon.]. .Iadd.β-D-ribofuranosyl .Iaddend.and R 1  is selected from the group consisting of ##STR9## (d) physiologically acceptable acid addition salts of (c), ##STR10## 
     
     
       2. A compound selected from the group consisting of 5'-phosphates and 3',5'-cyclic phosphates of a compound according to claim 1. 
     
     
       3. A compound selected from the group consisting of (I) compounds of structure: ##STR11## wherein .[.one of R 2  and.]. R 3  .[.are.]. .Iadd.is .Iaddend.hydroxyl.[., the other being.]. .Iadd.and R 2  is .Iaddend.hydrogen, and wherein R 1  is selected from the group consisting of ##STR12## (d) physiologicaly acceptable acid addition salts of (c), ##STR13## (II) a 5'-phosphate of a compound (I); and (III) a 3',5'-cyclic phosphate of a compound (I).  .[. 
     
     
       4.  A compound according to claim 3 wherein R 2  is hydrogen..]. 
     
     
       5. A compound according to claim .[.4.]. .Iadd.3 .Iaddend.wherein otherwise free glycosyl hydroxyls are acyl-blocked. 
     
     
       6. A compound according to claim .[.4.]. .Iadd.3 .Iaddend.wherein R 1  is (a), (b), (c) or (d). 
     
     
       7. A compound according to claim .[.4.]. .Iadd.3 .Iaddend.wherein R 1  is (a), (b) or (d). 
     
     
       8. The ammonium or alkali metal salt of a 5'-phosphate (II) according to claim 7.  .[.9. A compound according to claim 3 wherein R 3  is hydrogen..]. .[.10. A compound according to claim 9 wherein otherwise free glycosyl hydroxyls are acyl-blocked..].  .[.11. A compound according to claim 9 and wherein R 1  is (a), (b), (c) or (d)..]. .[.12. A compound according to claim 9 wherein R 1  is (a), (b) or (d)..]. .[.13. The ammonium or alkali metal salt of a 5'-phosphate (II) according to claim 
     
     
        12..]. 14. A compound (I) according to claim .[.4.]. .Iadd.3. .Iaddend. 
     
     
            A compound (II) according to claim .[.4.]. .Iadd.3. .Iaddend. 16. A compound (III) according to claim .[.4.]. .Iadd.3. .Iaddend. .[.17. A compound (I) according to claim 9..].  .[.18. A compound (II) according to 
     
     
        claim 9..].  .[.19. A compound (III) according to claim 9..]. 20. The ammonium salt of the 5'-phosphate of 
     
     
        1-(β-D-ribofuransoyl)-1,2,4-triazole-3-carboxamide. 
     
     
        21. 1(-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide. 
     
     
        22. 1-(β-D-ribofuranosyl)-1,2,4-triazole-3-thiocarboxamide. 
     
     
        23. 1-(β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamidine. 24. 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxa 
     
     
       mide. 25. 1-(β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide hydrochloride.  .[.26. 
     
     
        1-(β-D-xylofuranosyl)-1,2,4-triazole-3-carboxamide..]. 27. 1-(β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide 3',5'-cyclic 
     
     
        phosphate. 28. The ammonium salt of the compound of claim 27.