Imidazoquinoline derivatives and their use in therapy

1. A compound of formula (I):

wherein:

R 1 represents —O—Z—(P(═O)—OH)—O—Y-A

R 2 represents H, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkylC 1 -C 6 alkyl, C 3 -C 6 cycloalkylC 1 -C 6 alkylamino, C 3- -C 6 cycloalkylC 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 6 alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkylamino, C 1 -C 6 alkoxyC 1 -C 6 alkoxy; and optionally terminally substituted with a hydroxyl, amino, —NHNH 2 , N 3 , —C≡CH, —COOH, or maleimido group;

Z represents (C 2 -C 6 alkyleneO) q ;

Y represents (C 2 -C 6 alkyleneO) r ;

q represents an integer 1 to 6;

r represents 0 or an integer 1 to 20;

R 3 represents C 2 -C 6 alkylene-OH, C 2 -C 6 alkylene-NH 2 , C 2 -C 5 alkenyl-CH 2 —OH or C 2 -C 5 alkenyl-CH 2 —NH 2 ;

A represents

wherein:

R 4 represents H, C 4 -C 24 alkyl, C 4 -C 24 alkenyl, —CO—C 3 -C 23 alkyl, or —CO—C 3 -C 23 alkenyl;

R 5 represents C 4 -C 24 alkyl, C 4 -C 24 alkenyl, —CO—C 3 -C 23 alkyl, or —CO—C 3 -C 23 alkenyl;

p represents 0 or an integer 1 to 6;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein R 2 represents H, C 1 -C 6 alkyl or C 1 -C 6 alkoxyC 1 -C 6 alkyl.

3. The compound according to claim 1 wherein r represents 0 or an integer 1 to 3.

4. The compound according to claim 1 wherein R 3 represents C 2 -C 6 alkylene-OH.

5. The compound according to claim 1 wherein p represents an integer 1 to 3.

6. The compound according to claim 1 wherein A represents

7. The compound according to claim 1 which is a compound of formula (IA):

wherein:

R 1 represents —O—Z—O—(P(═O)—OH)—O—Y-A

R 2 represents H, C 1 -C 6 alkyl or C 1 -C 3 alkoxyC 1 -C 3 alkyl;

Z represents (C 2 -C 6 alkyleneO) q ;

Y represents (C 2 -C 6 alkyleneO) r ;

q represents an integer 1 to 6;

r represents 0 or an integer 1 to 20;

R 3 represents C 2 -C 6 alkylene-OH;

A represents

wherein:

R 4 represents H, —CO—C 3 -C 23 alkyl, or —CO—C 3 -C 23 alkenyl;

R 5 represents, —CO—C 3 -C 23 alkyl, or —CO—C 3 -C 23 alkenyl;

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 7 wherein R 2 represents H, n-butyl or CH 3 CH 2 OCH 2 —.

9. The compound according to claim 7 wherein Z represents CH 2 CH 2 O.

10. The compound according to claim 7 wherein Y represents ((CH 2 ) 2 O) r .

11. The compound according to claim 7 wherein q represents an integer 1 to 3.

12. The compound according to claim 7 wherein r represents 0 or an integer 1 to 6.

13. The compound according to claim 12 wherein R 3 represents —CH 2 CH 2 OH.

14. The compound according to claim 7 wherein R 4 represents H and R 5 represents —CO—C 3 -C 23 alkyl, or —CO—C 3 -C 23 alkenyl.

15. The compound according to claim 7 wherein R 4 and R 5 independently represent —CO—C 3 -C 23 alkyl or —CO—C 3 -C 23 alkenyl.

16. The compound according to claim 1 selected from:

and pharmaceutically acceptable salts thereof.

17. The compound according to claim 14 selected from

and pharmaceutically acceptable salts thereof.

18. An immunogenic composition comprising a compound according to claim 1 and a vaccine antigen.

19. A method of inducing an immune response in a mammal which comprises administering to said mammal in need thereof an immunostimulatory amount of a compound or composition according to claim 1 .

20. A method of inducing protective immunity against a disease in a mammal which comprises administering to a mammal in need thereof an immunostimulatory amount of a compound according to claim 1 together with a disease antigen.

21. A method of treatment of cancer in a mammal which comprises administering to a mammal in need thereof an immunostimulatory amount of a compound according to claim 1 together with a cancer antigen.

22. A method of preparing a choline salt of a compound according to claim 1 , comprising:

(a) dissolving the compound in an aqueous vehicle;

(b) adding the choline salt; and

(c) mixing the compound and choline salt;

wherein the method does not include the use of an organic solvent.

23. A method of preparing a choline salt of a compound according to claim 1 , comprising:

(a) dissolving the compound in an organic solvent;

(b) adding the choline salt;

(c) mixing the compound and choline salt; and

(d) removing the organic solvent,

wherein the method does not include a vacuum drying step.