2'-deoxy-4'-thioribonucleosides and their antiviral activity

• US 5,591,722 A
• Filed: 12/12/1994
• Issued: 01/07/1997
• Est. Priority Date: 09/15/1989
• Status: Expired due to Term

• Current Assignee: Southwest Research Institute
• Original Assignee: Southwest Research Institute
• Inventors: Secrist, John A. III, Montgomery, John A.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US08/354,313
• Time in Patent Office: 757 Days
• Field of Search: 536/4.1, 536/27.1, 536/27.13, 536/27.21, 536/27.6, 536/27.61, 536/27.63, 536/27.7, 536/27.81, 536/28.1, 536/28.5, 536/28.52, 536/28.53 , 536/28.54, 536/28.55, 549/30, 549/31, 549/33, 514/45, 514/46, 514/49, 514/50
• US Class Current: 514/45
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals

Abstract

2'"'"'-Deoxy-4'"'"'-thio-ribonucleosides, intermediates in their production, and their use as antiviral and anticancer agents are disclosed.

Claims

1. A compound having the formula ##STR31## wherein B is selected from the group consisting of ##STR32## wherein X_1-8 are selected from the group consisting of hydrogen, NH₂ and halogen;

wherein X₉ is selected from the group of hydrogen, methyl; and

X₁₀ is selected from the group consisting of hydrogen, methyl and halogen; and

wherein R¹ and R² are selected from the group of hydrogen, acyl protecting groups, and mixtures thereof.

2. A compound according to claim 1 wherein R¹ and R² are hydrogen.

3. A compound according to claim 1 wherein R¹ and R² are hydrogen.

4. A compound according to claim 1 which is 9-(2-deoxy-4-thio-α

-D-ribofuranosyl)-2-chloro-6-aminopurine.

5. A compound according to claim 1 which is 9-(2-deoxy-4-thio-α

-D-ribofuranosyl)-2,6-diaminopurine.

6. A compound according to claim 1 which is 9-(2-deoxy-4-thio-α

-D-ribofuranosyl)-2-amino-1,6-dihydro-6-oxopurine

7. A compound according to claim 1 which is 9-(2-deoxy-4-thio-α

-D-ribofuranosyl)-2-fluoro-6-aminopurine.

8. A compound according to claim 1 which is 9-(2-deoxy-4-thio-α

-D-ribofuranosyl)-6-aminopurine.

9. A compound according to claim 1 which is 9-(2-deoxy-4-thio-α

-D-ribofuranosyl)-1,6-dihydro-6-oxopurine.

10. A compound according to claim 1 which is 1-(2-deoxy-4-thio-α

-D-ribofuranosyl)uracil.

11. A compound according to claim 1 which is 2'"'"'-deoxy-4'"'"'-thiouridine.

12. A compound according to claim 1 which is 4'"'"'-thiothymidine.

13. A compound according to claim 1 which is 1-(2-deoxy-4-thio-α

-D-ribofuranosyl)thymine.

14. A compound according to claim 1 which is 1-(2-deoxy-4-thio-α

,β

-D-ribofuranosyl)cytosine.

15. A compound according to claim 1 which is 2'"'"'-deoxy-4'"'"'-thiocytidine.

16. A compound having the formula ##STR33## wherein B is a member selected from the group consisting of:

##STR34## wherein X_11-14 are selected from the group of H, CH3, and halogen, and R¹ and R² is selected from the group of hydrogen, acyl protecting groups, and mixtures thereof.

17. A compound having the formula ##STR35## wherein B is selected from the group consisting of pyrimidine and purine nucleoside bases with the provision that when B is pyrimidine, B is not a uracil molecule having a halogen at the C⁵ -heterocyclic carbon of the molecule;

and wherein R¹ and R² are selected from the group consisting of hydrogen, acyl protecting groups, and mixtures thereof.

18. A method for producing an antiviral effect against a virus that replicates in a virus-infected mammalian cell which method comprises contacting said cell with a compound according to the formula ##STR36## wherein B is selected from the group consisting of ##STR37## wherein X_1-8 are selected from the group consisting of hydrogen, NH₂ and halogen;

wherein X₉ is selected from the group consisting of hydrogen, methyl;

wherein X₁₀ is selected from the group consisting of hydrogen, methyl and halogen; and

wherein R¹ and R² are selected from the group of hydrogen, acyl protecting groups, and mixtures thereof;

said virus being herpes simplex virus or human cytomegalovirus.

19. A method according to claim 18 wherein the virus is a herpes simplex virus.

20. A method according to claim 18 wherein the antiviral effect is the inhibition of cytopathogenic effects produced by herpes simplex virus type 1, and wherein the compound is selected from the group consisting of 4'"'"'-thiothymidine and 1-(2-deoxy-4-thio-62-D-ribofuranosyl)thymine.

21. A method according to claim 18 wherein the antiviral effect is the inhibition of cytopathogenic effects produced by the human cytomegalovirus, and wherein the compound is 4'"'"'-thiothymidine.