1,2,4-Triazole nucleosides

• US RE29,835 E
• Filed: 03/28/1977
• Issued: 11/14/1978
• Est. Priority Date: 06/01/1971
• Status: Expired due to Term

• Current Assignee: Viratek, Inc. (Bausch Health Cos., Inc.)
• Original Assignee: ICN Pharmaceuticals, Inc (Bausch Health Cos., Inc.)
• Inventors: Robins, Roland K., Witkowski, Joseph T.
• Primary Examiner(s): Brown, Johnnie R.
• Application Number:
  US05/782,294
• Time in Patent Office: 596 Days
• Field of Search: 536/23, 536/29
• US Class Current: 536/26.11
• CPC Class Codes: C07H 13/04 having the esterifying carboxyl radicals attached to acyclic carbon atoms
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/056 Triazole or tetrazole radicals

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.

Claims

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 R₁ 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 R₂ and.]. R₃ .[.are.]. .Iadd.is .Iaddend.hydroxyl.[., the other being.]. .Iadd.and R₂ is .Iaddend.hydrogen, and wherein R₁ 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 R₂ 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 R₁ is (a), (b), (c) or (d).

7. A compound according to claim .[.4.]. .Iadd.3 .Iaddend.wherein R₁ 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 R₃ 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 R₁ is (a), (b), (c) or (d)..]. .[.12. A compound according to claim 9 wherein R₁ is (a), (b) or (d)..]. .[.13. The ammonium or alkali metal salt of a 5'"'"'-phosphate (II) according to claim

9. 12..]. 14. A compound (I) according to claim .[.4.]. .Iadd.3. .Iaddend.

11. claim 9..]. .[.19. A compound (III) according to claim 9..]. 20. The ammonium salt of the 5'"'"'-phosphate of

12. 1-(β

-D-ribofuransoyl)-1,2,4-triazole-3-carboxamide.

13. 21. 1(-β

-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide.

14. 22. 1-(β

-D-ribofuranosyl)-1,2,4-triazole-3-thiocarboxamide.

15. 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

16. mide. 25. 1-(β

-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide hydrochloride. .[.26.

17. 1-(β

-D-xylofuranosyl)-1,2,4-triazole-3-carboxamide..]. 27. 1-(β

-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide 3'"'"',5'"'"'-cyclic

18. phosphate. 28. The ammonium salt of the compound of claim 27.

10. 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