Therapeutic phosphonate compounds

• US 20060264404A1
• Filed: 10/25/2005
• Published: 11/23/2006
• Est. Priority Date: 04/25/2003
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Prasad, Vidya K., 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., Hirschmann, Ralph F., Jin, Haolun, Sherlock, Rosemarie, Zhang, Jennifer R., Lee, William A., Pyun, Hyung-Jung, Mackman, Richard L., Kirschberg, Thorsten A., Gibbs, Craig S., Nelson, Peter H., Cannizzaro, Carina E., Krawczyk, Steven, Desai, Manoj
• Granted Patent: US 7,645,747 B2
• Time in Patent Office: Days
• US Class Current: 514/80
• 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 comprising a therapeutic compound linked to one or more phosphonate groups;

or a pharmaceutically acceptable salt or solvate thereof.

2. The conjugate of claim 1 wherein the therapeutic compound is an anti-inflammatory compound.

3. The conjugate of claim 1 wherein the therapeutic compound is a purine nucleoside phosphorylase inhibitor.

4. The conjugate of claim 1 wherein the therapeutic compound is an anti-cancer compound.

5. The conjugate of claim 1 wherein the therapeutic compound is active against immune-mediated conditions.

6. The conjugate of claim 1 wherein the therapeutic compound is active against metabolic diseases.

7. The conjugate of claim 1 wherein the therapeutic compound is an antiviral compound.

8. The conjugate of claim 1 wherein the therapeutic compound is a nucleoside or nucleoside analog.

9. The conjugate of claim 1 wherein the therapeutic compound is a kinase inhibitor.

10. The conjugate of claim 1 wherein the therapeutic compound is an antimetabolite.

11. The conjugate of claim 1 wherein the therapeutic compound is an IMPDH inhibitor.

12. The conjugate of claim 1 wherein the therapeutic compound is an anti-infective compound.

13. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

14. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

15. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

16. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

17. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

18. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

19. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

20. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

21. The conjugate of claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound of one of the following formulae:

22. The conjugate of claim 1 which has any one of the following formulae:

23. The conjugate of claim 1 which has one of the following formulae:

24. The conjugate of claim 1 which has one of the following formulae:

25. The conjugate of claim 1 which has one of the following formulae:

26. The conjugate oclaim 1 which has one of the following formulae:

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

87. A pharmaceutical composition comprising a pharmaceutical excipient and a conjugate as described in any one of claims 1-26.

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

and a pharmaceutically acceptable excipient.

27-85. -85. (canceled)

89-97. -97. (canceled)