Acyclic nucleoside phosphonate diesters

• US 10,195,222 B2
• Filed: 11/14/2017
• Issued: 02/05/2019
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Hostetler, Karl Y., Beadle, James R., Valiaeva, Nadejda
• Primary Examiner(s): Yoo, Sun Jae
• Application Number:
  US15/812,814
• Publication Number:
  US 20180064737A1
• Time in Patent Office: 448 Days
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07F 9/6512 having the nitrogen atoms in positions 1 and 3
• CPC Class Codes: C07F 9/65583 each of the hetero rings containing nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C07F 9/65616 containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present disclosure relates, inter alia, to compositions and methods for treating viral diseases and cancer. There are disclosed lipophilic antiviral and anticancer acyclic nucleoside phosphonate diesters, preparation thereof, and methods of using the compounds to treat viral diseases and cancer.

Claims

1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1, wherein L is octadecyloxyethyl.

3. The compound of claim 1, wherein L is hexadecyloxypropyl.

4. The compound of claim 1, wherein B_Nuc is guanine.

5. The compound of claim 1, wherein B_Nuc is adenine.

6. The compound of claim 1, wherein B_Nuc is cytosine, thymine, or uracil.

7. The compound of claim 1, wherein B_Nuc is 2,6-diaminopurine.

8. The compound of claim 4, wherein L is octadecyloxyethyl.

9. The compound of claim 4, wherein L is hexadecyloxypropyl.

10. The compound of claim 1, wherein the compound of Formula (I) is:

11. The compound of claim 1, wherein the compound of Formula (I) is:

12. The compound of claim 1, wherein the compound of Formula (I) is:

13. The compound of claim 1, wherein the compound of Formula (I) is:

14. A pharmaceutical composition comprising an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14 in a dosage form.

16. The pharmaceutical composition of claim 15, wherein the dosage form is a topical dosage form.

17. The pharmaceutical composition of claim 16, wherein the topical dosage form is a cream.

18. The pharmaceutical composition of claim 16, wherein the topical dosage form is a gel.

19. The pharmaceutical composition of claim 16, where the topical dosage form is an ointment.

20. The pharmaceutical composition of claim 15, wherein the dosage form is an oral dosage form.

21. The pharmaceutical composition of claim 20, wherein the oral dosage form is a pill or tablet.

22. A method of treating a human papilloma virus in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 or the pharmaceutically acceptable salt thereof to treat the human papilloma virus.

23. The method of claim 22, wherein the human papilloma virus is human papilloma virus type 16.

24. The method of claim 22, wherein the human papilloma virus is human papilloma virus type 18.

25. The method of claim 22, wherein the subject is a human.

26. A method of treating a human papilloma virus in a subject in need thereof, the method comprising topically administering to the subject a therapeutically effective amount of a topical dosage formulation comprising the compound of claim 1 or the pharmaceutically acceptable salt thereof to treat the human papilloma virus.

27. A compound of the formula:

28. A topical dosage formulation comprising the compound of claim 27 and a pharmaceutically acceptable carrier.

29. The formulation of claim 28, wherein the topical dosage formulation is a cream, a gel, or an ointment.

30. A method of treating human papilloma virus in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of claim 27 or the pharmaceutically acceptable salt thereof.

31. The method of claim 30, wherein the human papilloma virus is human papilloma virus type 16.

32. The method of claim 30, wherein the human papilloma virus is human papilloma virus type 18.

33. The method of claim 30, wherein the subject is a human.

34. A method of treating a human papilloma virus in a subject in need thereof, the method comprising topically administering to the subject a therapeutically effective amount of a topical dosage formulation comprising the compound of claim 27 or the pharmaceutically acceptable salt thereof to treat the human papilloma virus.