Acyclic nucleoside phosphonate diesters

Patent metadata

Field	Value
Publication number	US-10449207-B2
Application number	US-201816111378-A
Country	US
Kind code	B2
Filing date	Aug 24, 2018
Priority date	Mar 15, 2013
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

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.

First claim

What is claimed is:

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

wherein:
B Nuc is guanine, adenine, cytosine, thymine, uracil, or 2,6-diaminopurine;
L a is —(CH 2 ) 1-6 O(CH 2 ) 11-21 CH 3 ;
R a is selected from aryl, heteroaryl, heterocycloalkyl, aryl(C 1-6 alkyl), heteroaryl(C 1-6 alkyl), and heterocycloalkyl(C 1-6 alkyl); and
X a is hydrogen.

2. The compound of claim 1 , wherein L a is —(CH 2 ) 2 O(CH 2 ) 17 CH 3 .

3. The compound of claim 1 , wherein L a is —(CH 2 ) 3 O(CH 2 ) 15 CH 3 .

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 —(CH 2 ) 2 O(CH 2 ) 17 CH 3 .

10. The compound of claim 8 , wherein L a is —(CH 2 ) 3 O(CH 2 ) 15 CH 3 .

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 —(CH 2 ) 2 O(CH 2 ) 17 CH 3 .

14. The compound of claim 12 , wherein L a is —(CH 2 ) 3 O(CH 2 ) 15 CH 3 .

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.

Assignees

• Univ California

Inventors

• Hostetler Karl Y
• Beadle James R
• Valiaeva Nadejda

Classifications

• A61P31/22

  for herpes viruses · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P31/18

  for HIV · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P31/12

  Antivirals · CPC title