Therapeutic valine esters of acyclovir and pharmaceutically acceptable salts thereof

• US 4,957,924 A
• Filed: 08/04/1988
• Issued: 09/18/1990
• Est. Priority Date: 08/15/1987
• Status: Expired due to Term

• Current Assignee: Burroughs Wellcome and Co.
• Original Assignee: Burroughs Wellcome and Co.
• Inventors: Beauchamp, Lilia M.
• Primary Examiner(s): BERCH, MARK L
• Application Number:
  US07/228,377
• Time in Patent Office: 775 Days
• Field of Search: 544/276, 514/262
• US Class Current: 514/263.38
• CPC Class Codes: C07D 473/00 Heterocyclic compounds containing purine ring systems

Abstract

The present invention relates to certain amino acid exters of the purine nucleoside acyclovir, pharmaceutically acceptable salts thereof and their use in the treatment of herpes virus infections. The invention also includes pharmaceutical formulations and processes for the preparation of such compounds.

Claims

1. A pharmaceutically acceptable salt of 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate.

2. The salt of claim 1, which is an acid addition salt.

3. The salt of claim 1, which is derived from hydrochloric, sulfuric, phosphoric, maleic, fumaric, citric, tartaric, lactic, acetic or p-toluenesulfonic acid.

4. A pharmaceutical composition for use as an antiviral comprising an effective antiviral amount of the compound 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefor.

5. The composition of claim 4, in which the salt is an acid addition salt.

6. The composition of claim 4, in which the salt is the hydrochloride salt.

7. A tablet or capsule for use as an antiviral comprising an effective antiviral amount of the compound 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefor.

8. The tablet or capsule of claim 7, in which the salt is an acid addition salt.

9. The tablet or capsule of claim 7, in which the salt is the hydrochloride salt.

11. The method of claim 8, in which the salt is an acid addition salt.

12. The method of claim 11, in which the salt is the hydrochloride salt.

10. A method of treating a herpes virus infection in a human comprising administering to said human an effective herpes virus infection treatment amount of the compound 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof.

13. A method of treating a herpes virus infection in a human comprising orally administering to said human an effective herpes virus treatment amount of the compound 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof.

14. The method of claim 13, in which the herpes virus infection is a herpes simplex or herpes zoster infection.

15. A method of treating a hepatitis B virus or Epstein Barr virus infection in a human, which comprises administering to said human an effective hepatitis B virus or Epstein Barr virus infection treatment amount of the compound 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof.

16. The method of claim 15, in which the salt is an acid addition salt.

17. 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate hydrochloride.

18. 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate.

19. A method of generating acyclovir in the plasma of a mammal, which comprises orally administering the compound 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof to said mammal.

20. The method of claim 19, in which an acid addition salt is orally administered.

21. The method of claim 19, in which the hydrochloride salt is orally administered.

22. The hydrochloride salt of 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate.

23. The method of treating a CMV infection in a human, which comprises administering to said human an effective CMV treatment amount of 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate or a pharmaceutically acceptable salt thereof.

24. The method of claim 23, in which the salt is an acid addition salt.