L-nucleosides

• US 5,587,362 A
• Filed: 01/28/1994
• Issued: 12/24/1996
• Est. Priority Date: 01/28/1994
• Status: Expired due to Term

• Current Assignee: The University of Georgia Research Foundation, Inc., Yale University
• Original Assignee: The University of Georgia Research Foundation, Inc., Yale University
• Inventors: Cheng, Yung-Chi, Chu, Chung K., Pai, Balakrishna S., Yao, Gang-Qing
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US08/189,070
• Time in Patent Office: 1,061 Days
• Field of Search: 514/49, 514/50, 514/45, 514/46, 514/47, 536/28.54, 536/28.55, 536/26.26, 536/26.7, 536/26.8, 536/27.6, 536/28.5, 424/420, 424/457
• US Class Current: 514/46
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

A compound, and a pharmaceutical composition comprising an effective mount to treat HBV or EBV of a compound, of the formula: ##STR1## wherein R is selected from the group consisting of 5-methyluracil, adenine and cytosine, and R'"'"' is hydrogen, acyl, or alkyl or a monophosphate, diphosphate or triphosphate ester, or its pharmaceutically acceptable salt.

Claims

1. A compound of the formula:

##STR3## wherein R is selected from the group consisting of 5-methyluracil, adenine and cytosine, and R'"'"' is selected from the group of hydrogen, acyl, or alkyl or a monophosphate, diphosphate or triphosphate ester.

2. The compound of claim 1, wherein the compound is 2'"'"'-fluoro-5-methyl-β

-L-arabinofuranosyluridine.

3. The compound of claim 1, wherein R is selected from group consisting of adenine and cytosine.

4. The compound of claim 1, wherein R is 5-methyluracil.

5. The compound of claim 1, wherein R'"'"' is a phosphate ester.

6. The compound of claim 1, wherein R'"'"' is hydrogen.

7. The compound of claim 1, wherein R'"'"' is alkyl.

8. The compound of claim 1, wherein R'"'"' is acyl.

9. The compound of claim 1 that is at least 95% free of the corresponding D-enantiomer.

10. The compound of claim 1 that is at least 98% free of the corresponding D-enantiomer.

11. The compound of claim 4, wherein R'"'"' is a phosphate ester.

12. The compound of claim 4, wherein R'"'"' is alkyl.

13. The compound of claim 4, wherein R'"'"' is acyl.

14. The compound of claim 4 that is at least 95% free of the corresponding D-enantiomer.

15. The compound of claim 4 that is at least 98% free of the corresponding D-enantiomer.

16. The compound of claim 3 that is at least 95% free of the corresponding D-enantiomer.

17. The compound of claim 3 that is at least 98% free of the corresponding D-enantiomer.

18. A compound of the formula:

##STR4## wherein R is adenine or cytosine, and R'"'"' is hydrogen, acyl, or alkyl or a monophosphate, diphosphate or triphosphate ester.

19. A compound of the formula:

##STR5## wherein R is 5-methyluracil and R'"'"' is hydrogen, acyl, or a monophosphate, diphosphate or triphosphate ester.

20. A pharmaceutical composition comprising an effective amount to treat HBV of 2'"'"'-fluoro-5-methyl-β

-L-arabinofuranosyluridine in with a pharmaceutically acceptable carrier.

37. The pharmaceutical composition of claim 20, wherein the pharmaceutically acceptable carrier is a controlled release formulation.

21. A pharmaceutical composition comprising an effective amount to treat HBV of a compound of the formula:

##STR6## wherein R is selected from the group consisting adenine end cytosine, and R'"'"' is hydrogen, acyl, or alkyl or a monophosphate, diphosphates or triphosphate ester, or its pharmaceutically acceptable salt, in combination with a pharmaceutically acceptable carrier.

22. The pharmaceutical composition of claim 21, wherein R is 5-methyluracil.

23. The pharmaceutical composition of claim 21, wherein R is adenine.

24. The pharmaceutical composition of claim 21, wherein R is cytosine.

25. The pharmaceutical composition of claim 21, wherein the compound is at least 95% free of the corresponding D-enantiomer.

26. The pharmaceutical composition of claim 21, wherein the compound is at least 98% free of the corresponding D-enantiomer.

27. The pharmaceutical composition of claim 21, wherein R'"'"' is a phosphate ester.

28. The pharmaceutical composition of claim 21, wherein R'"'"' is alkyl.

29. The pharmaceutical composition of claim 21, wherein R'"'"' is acyl.

30. The pharmaceutical composition of claim 22 that is at least 95% free of the that is at least 95% free of the corresponding D-enantiomer.

31. The pharmaceutical composition of claim 22 that is at least 98% free of the corresponding D-enantiomer.

32. The pharmaceutical composition of claim 23 or 24 that is at least 95% free of the corresponding D-enantiomer.

33. The pharmaceutical composition of claim 21, wherein the pharmaceutically acceptable carrier is suitable for oral delivery.

34. The pharmaceutical composition of claim 22, wherein the pharmaceutically acceptable carrier is suitable for oral delivery.

35. The pharmaceutical composition of claim 21, wherein the pharmaceutically acceptable carrier is a liposomal suspension.

36. The pharmaceutical composition of claim 22, wherein the pharmaceutically acceptable carrier is a liposomal suspension.

38. The pharmaceutical composition of claim 21, wherein the pharmaceutically acceptable carrier is a controlled release formulation.