Acyclic nucleoside phosphonate diesters

• US 10,449,207 B2
• Filed: 08/24/2018
• Issued: 10/22/2019
• 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): Kifle, Bruck
• Application Number:
  US16/111,378
• Publication Number:
  US 20180360859A1
• Time in Patent Office: 424 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 (Ia), or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1, wherein L^a is —

(CH₂)₂O(CH₂)₁₇CH₃.

3. The compound of claim 1, wherein L^a is —

(CH₂)₃O(CH₂)₁₅CH₃.

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

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

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

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

8. The compound of claim 1, wherein R^a is aryl(C_1-6 alkyl).

9. The compound of claim 8, wherein L^a is —

(CH₂)₂O(CH₂)₁₇CH₃.

10. The compound of claim 8, wherein L^a is —

(CH₂)₃O(CH₂)₁₅CH₃.

11. The compound of claim 8, wherein aryl(C_1-6 alkyl) is benzyl.

12. The compound of claim 1, wherein R^a is aryl.

13. The compound of claim 12, wherein L^a is —

(CH₂)₂O(CH₂)₁₇CH₃.

14. The compound of claim 12, wherein L^a is —

(CH₂)₃O(CH₂)₁₅CH₃.

15. The compound of claim 12, wherein aryl is phenyl.

16. A pharmaceutical composition comprising an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16, in a topical dosage form.

18. The pharmaceutical composition of claim 17, in a cream, a gel, or an ointment.

19. A method of treating a disorder selected from the group consisting of human papilloma virus, cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, and anal intraepithelial neoplasia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

20. The method of claim 19, wherein the disorder is human papilloma virus.

21. The method of claim 20, wherein the human papilloma virus is human papilloma virus type 52, type 58, type 16, type 18, or type 11.

22. The method of claim 19, wherein the disorder is cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, or anal intraepithelial neoplasia.

23. The method of claim 19, wherein the subject is a human.