Quinone based nitric oxide donating compounds for ophthalmic use

1. A method for treating age related macular degeneration, diabetic retinopathy, macular degeneration, inflammatory retinal disease, and/or uveitis comprising administering to a patient in need thereof a compound of formula (I) or stereoisomers 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 O, S or is —CHONO 2 , with the proviso that when X is —CHONO 2 then m is 0.

2. The method according to claim 1 , wherein Q is

wherein m, p, X are as defined above.

3. The method according to claim 2 , wherein the compound of formula (I) is represented by formula (Ib)

wherein n, m, p, X are as defined above.

4. The method according to claim 2 , wherein the compound of formula (I) is represented by formula (Ic)

wherein n, m, p, X are as defined above.

5. The method according to claim 2 , wherein the compound of formula (I) is represented by formula (Id)

wherein n, m, p, X are as defined above.

6. The method according to claim 2 , wherein the compound of formula (I) is represented by formula (Ie)

wherein n, m, p, X are as defined above.

7. The method according to claim 2 , wherein the compound of formula (I) is represented by formula (If)

wherein n, m, p, X are as defined above.

8. The method according to claim 2 , wherein p is 0.

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

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

11. The method according to claim 1 , wherein Q is

12. The method according to claim 11 , wherein the compound of formula (I) is represented by formula (Ig)

wherein n is an integer from 0 to 10.

13. The method according to claim 11 , wherein the compound of formula (I) is represented by formula (Ih)

wherein n is an integer from 0 to 10.

14. The method according to claim 1 , wherein the compound of formula (I) is represented by formula (Ii)

wherein

n is an integer from 0 to 6.

15. The method according to claim 1 , wherein the compound of formula (I) is represented by formula (II)

wherein

n is an integer from 0 to 6.

16. The method according to claim 1 , wherein the compound of formula (I) is represented by formula (Im)

wherein

n is an integer from 0 to 6.

17. The method according to claim 1 wherein the compound of formula (I) is selected from the group consisting of:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

10-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)decyl nitrate (Compound (13)) 4-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)butyl nitrate (Compound (22))

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

18. The method according to claim 1 , wherein the compound of formula (I) is 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)decyl nitrate (Compound (6)).

19. A compound of formula (I) as defined in claim 1 , which is formulated for topical, periocular or intraocular administration.