Quinone based nitric oxide donating compounds

1. A compound of formula (I)

or steroisomers thereof, wherein

R 1 is selected from H, methyl, methoxy;

R 3 is selected from H, methyl, methoxy;

or R 1 and R 3 together form —CH═CH—CH═CH—;

R 2 is H, methyl;

n is an integer from 0 to 10;

Q is selected from the group consisting of:

wherein

m is an integer from 0 to 6;

p is an integer from 0 to 1;

X is 0, S or is —CHONO 2 , with the proviso that when X is —CHONO 2 then m is 0.

2. A compound according to claim 1 , wherein Q is

wherein m, p, X are as defined in claim 1 .

3. A compound according to claim 2 , wherein the compound is of formula (Ib)

wherein n, m, p, X are as defined in claim 1 .

4. A compound according to claim 2 , wherein the compound is of formula (Ic)

wherein n, m, p, X are as defined in claim 1 .

5. A compound according to claim 2 , wherein the compound is of formula (Id)

wherein n, m, p, X are as defined in claim 1 .

6. A compound according to claim 2 , wherein the compound is of formula (Ie)

wherein n, m, p, X are as defined in claim 1 .

7. A compound according to claim 2 , wherein the compound is of formula (If)

wherein n, m, p, X are as defined in claim 1 .

8. A compound according to claim 2 , wherein p is 0.

9. A compound according to claim 2 , wherein p is 1 and X is O or S.

10. A compound according to claim 2 , wherein p is 1, X is —CHONO 2 and m is 0.

11. A compound according to claim 1 , wherein Q is

12. A compound according to claim 11 , wherein the compound is of formula (Ig)

wherein n is an integer from 0 to 10.

13. A compound according to claim 11 , wherein the compound is of formula (Ih)

wherein n is an integer from 0 to 10.

14. A compound according to claim 1 , wherein the compound is of formula (Ii)

wherein

n is an integer from 0 to 6.

15. A compound according to claim 1 , wherein the compound is of formula (II)

wherein

n is an integer from 0 to 6.

16. A compound according to claim 1 , wherein the compound is of formula (Im)

wherein

n is an integer from 0 to 6.

17. A compound according to claim 1 selected from the group consisting of:

1) 5-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)pentyl nitrate (Compound (1)),

2) 5-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)pentyl nitrate (compound (2)),

3) 5-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)pentyl nitrate (Compound (12)),

4) 6-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)hexyl nitrate (compound (15)),

5) 4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butyl nitrate (compound (3)),

6) 5-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)pentane-1,2-diyl dinitrate (compound (10)),

7) 3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)propyl nitrate (compound (8)),

8) 6-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)hexyl nitrate (compound (16)),

9) 4-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)butyl nitrate (compound (4)),

10) 11-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)undecane-1,2-diyl dinitrate (Compound (17)),

11) 11-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)undecan-2-yl nitrate (Compound (18)),

12) 3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)propane-1,2-diyl dinitrate (Compound (9)),

13) 3-(3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)propoxy)propyl nitrate (Compound (14)),

14) 2-(3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)propoxy)ethyl nitrate (Compound (20)),

15) 6-(3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)propylthio)hexyl nitrate (Compound (21)),

16) 10-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)decyl nitrate (Compound (13)),

17) 4-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)butyl nitrate (Compound (22)),

18) 6-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)hexyl nitrate (Compound (23)),

19) 3-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)propyl nitrate (Compound (24)),

20) 3-(3-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)propoxy) propyl nitrate (Compound (25)),

21) 3-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)propane-1,2-diyl dinitrate (Compound (27),

22) 6-(5-methoxy-2,4-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)hexyl nitrate (Compound (28)),

23) 6-(4-methoxy-2,5-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)hexyl nitrate (Compound (29)),

24) 10-(4-methoxy-2,5-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)decyl nitrate (Compound (30)),

25) 10-(5-methoxy-2,4-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)decyl nitrate (Compound (31)),

26) 8-(4-methoxy-2,5-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)octyl nitrate (Compound (32)),

27) 8-(5-methoxy-2,4-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)octyl nitrate (Compound (19)),

28) 10-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)decyl nitrate (Compound (5)),

29) 8-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)octyl nitrate (compound (33)),

30) 8-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)octyl nitrate (Compound (34)),

31) 2-[2-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)ethyl]-4-(nitrooxy)tetrahydrofuran-3-yl-nitrate (Compound (35)),

32) 2-[2-(1,4-dimethoxy-3-methyl-naphthalen-2-yl)-ethyl]-3,4-bis-nitrooxy-tetrahydro-furan (Compound (36) and (37)),

33) 3-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)propyl nitrate (Compound (7)),

34) 5-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)pentane-1,2-diyl dinitrate (Compound (11)), and

35) 10-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)decane-1,2-diyl dinitrate (Compound (26)).

18. A compound according to claim 1 , which is 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)decyl nitrate (Compound (6)).

19. A method of treating pulmonary arterial hypertension comprising administering the compound according to claim 1 to a patient in need thereof.

20. A method of treating systemic sclerosis and scleroderma comprising administering the compound according to claim 1 to a patient in need thereof.

21. A method of treating muscular dystrophies comprising administering the compound according to claim 1 to a patient in need thereof.

22. A method of treating Duchenne's muscular dystrophy and Becker's muscular dystrophy comprising administering the compound according to claim 1 to a patient in need thereof.

23. A method of treating vascular dysfunctions associated with hypertension comprising administering the compound according to claim 1 to a patient in need thereof.

24. A method of treating glaucoma and ocular hypertension comprising administering the compound according to claim 1 to a patient in need thereof.

25. A method of treating ocular hypertension comprising administering the compound according to claim 1 to a patient in need thereof.

26. Pharmaceutical composition comprising at least a compound according to claim 1 and pharmaceutically acceptable excipients.

27. Pharmaceutical composition comprising the compound of claim 18 and pharmaceutically acceptable excipients.

28. A composition comprising a compound of formula (I) as defined in claim 1 and one or more further active ingredients selected from the group consisting of alpha adrenergic agonists, beta blockers, carbonic anhydrase inhibitors, bimatoprost, latanoprost, travoprost, unoprostone, tafluprost, non-steroidal anti-inflammatory drugs, or steroidal anti-inflammatory drugs.