Therapeutic phosphonate compounds

• US 7,645,747 B2
• Filed: 10/25/2005
• Issued: 01/12/2010
• Est. Priority Date: 04/25/2003
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Prasad, Vidya K., Hirschmann, Ralph F., Sherlock, Rosemarie, Gibbs, Craig S., Krawczyk, Steven, Desai, Manoj, Watkins, William J., Zhang, Lijun, Cho, Aesop, Fardis, Maria, Markevitch, David Y., Chong, Lee S., Kim, Choung U., Lin, Kuei-Ying, Boojamra, Constantine G., Ray, Adrian S., Lee, Christopher P., Chen, Xiaowu, Swaminathan, Sundaramoorthi, Chen, James M., Huang, Alan X., Oare, David A., Jin, Haolun, Zhang, Jennifer R., Lee, William A., Pyun, Hyung-Jung, Mackman, Richard L., Kirschberg, Thorsten A., Nelson, Peter H., Cannizzaro, Carina E.
• Primary Examiner(s): Anderson; Rebecca L
• Assistant Examiner(s): Young; Shawquia
• Application Number:
  US11/258,621
• Publication Number:
  US 20060264404A1
• Time in Patent Office: 1,540 Days
• Field of Search: 558/168
• US Class Current: 514/112
• CPC Class Codes: C07F 9/4006 Esters of acyclic acids which can have further substituents on alkyl
• CPC Class Codes: C07F 9/4465 of aliphatic amines
• CPC Class Codes: C07F 9/5304 Acyclic saturated phosphine oxides or thioxides
• CPC Class Codes: C07F 9/650952 having the nitrogen atoms in the positions 1 and 4
• CPC Class Codes: C07F 9/653 Five-membered rings
• CPC Class Codes: C07F 9/65507 condensed with carbocyclic rings or carbocyclic ring systems
• CPC Class Codes: C07F 9/65515 the oxygen atom being part of a five-membered ring
• CPC Class Codes: C07F 9/65517 condensed with carbocyclic rings or carbocyclic ring systems
• CPC Class Codes: C07F 9/65583 each of the hetero rings containing nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/65586 at least one of the hetero rings does not contain 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

Abstract

The invention is related to phosphorus substituted therapeutic agents, compositions containing such phosphorus substituted agents, and therapeutic methods that include the administration of such phosphorus substituted agents, as well as to processes and intermediates useful for preparing such agents.

Claims

1. A conjugate that is a compound of the following formula:

2. The conjugate as described in claim 1, which is isolated and purified.

3. A pharmaceutical composition comprising a pharmaceutical excipient and a conjugate as described in claim 1.

4. A unit dosage form comprising a conjugate as described in claim 1;

and a pharmaceutically acceptable excipient.

5. The conjugate of claim 1 which has the formula:

6. The conjugate of claim 1 wherein each A³ is of the formula:

7. The conjugate of claim 1 wherein each A³ is of the formula:

8. The conjugate of claim 1 wherein each A³ is of the formula:

9. The conjugate of claim 1 wherein each A³ is of the formula:

10. The conjugate of claim 1 wherein each A³ is of the formula:

11. The conjugate of claim 1 wherein each A³ is of the formula:

12. The conjugate of claim 1 wherein each A³ is of the formula:

13. The conjugate of claim 1 wherein each A³ is of the formula:

14. The conjugate of claim 1 wherein each A³ is of the formula:

16. The conjugate of claim 1 wherein each A³ is of the formula:

17. The conjugate of claim 1 wherein each A³ is of the formula:

18. The conjugate of claim 1 wherein each A³ is of the formula:

19. The conjugate of claim 1 wherein each A³ is of the formula:

20. The conjugate of claim 1 wherein each A³ is of the formula:

21. The conjugate of claim 1 wherein each A³ is of the formula:

22. The conjugate of claim 1 wherein each A³ is of the formula:

23. The conjugate of claim 1 wherein each A³ is of the formula:

24. The conjugate of claim 1 wherein each A³ is of the formula:

25. The conjugate of claim 1 wherein each A³ is of the formula:

26. The conjugate of claim 1 wherein each A³ is of the formula:

27. The conjugate of claim 1 wherein each A³ is of the formula:

28. The conjugate of claim 1 wherein each A³ is of the formula:

29. The conjugate of claim 1 wherein A⁰ is of the formula:

15. The conjugate of claimi wherein each A³ is of the formula: