Compounds and compositions for the treatment of ocular disorders

1. A compound of Formula XVI:

or a pharmaceutically acceptable salt thereof;

wherein:

R 33 is selected from: carbonyl linked polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid,

R 31 is selected from hydrogen, A, —C(O)A, aryl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, arylalkyl, heteroaryl, and heteroarylalkyl;

A is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, and alkyloxy; and

x is independently selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.

2. The compound of claim 1 , wherein x is selected from the group consisting of 1, 2, 3, 4, and 5.

3. The compound of claim 1 , wherein x is selected from the group consisting of 6, 7, 8, 9, and 10.

4. The compound of claim 1 , wherein R 31 is —C(O)A and A is methyl.

5. The compound of claim 1 , wherein R 31 is hydrogen.

6. The compound of claim 1 , wherein R 33 is

7. The compound of claim 6 , wherein x is 1, 2, or 3.

8. The compound of claim 6 , wherein R 31 is hydrogen.

9. The compound of claim 6 , wherein R 31 is —C(O)A and A is methyl.

10. The compound of claim 6 , wherein x is 4, 5, or 6.

11. The compound of claim 10 , wherein R 31 is hydrogen.

12. The compound of claim 10 , wherein R 31 is —C(O)A and A is methyl.

13. The compound of claim 6 , wherein x is 7, 8, 9, or 10.

14. The compound of claim 13 , wherein R 31 is hydrogen.

15. The compound of claim 13 , wherein R 31 is —C(O)A and A is methyl.

16. The compound of claim 1 , wherein R 33 is

17. The compound of claim 16 , wherein x is selected from 1, 2, 3, 4, and 5.

18. The compound of claim 16 , wherein x is selected from 6, 7, 8, 9, and 10.

19. The compound of claim 16 , wherein R 31 is hydrogen.

20. The compound of claim 16 , wherein R 31 is —C(O)A and A is methyl.

21. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

22. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

23. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

24. A compound of Formula XVI:

or a pharmaceutically acceptable salt thereof;

wherein:

R 33 is selected from:

R 31 is

and

x is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30.

25. The compound of claim 24 , wherein x is selected from 1, 2, 3, 4, and 5.

26. The compound of claim 24 , wherein x is selected from 6, 7, 8, 9, 10, and 11.

27. The compound of claim 24 , wherein R 33 is

28. The compound of claim 27 , wherein x is selected from 1, 2, and 3.

29. The compound of claim 27 , wherein x is selected from 4, 5, and 6.

30. The compound of claim 27 , wherein x is selected from 7, 8, 9, 10, and 11.

31. The compound of claim 24 , wherein x is

32. The compound of claim 31 , wherein x is selected from 1, 2, 3, 4, and 5.

33. The compound of claim 31 , wherein x is selected from 6, 7, 8, 9, 10, and 11.

34. A pharmaceutical composition comprising a compound of claim 1 in a pharmaceutically acceptable carrier.

35. A pharmaceutical composition comprising a compound of claim 24 in a pharmaceutically acceptable carrier.

36. A method for the treatment of an ocular disorder treatable with a beta-blocker comprising administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of claim 1 to a host in need thereof wherein the disorder is selected from glaucoma, age-related macular degeneration (AMD), a disorder related to an increase in intraocular pressure (TOP), a disorder related to neuroprotection, diabetic retinopathy, and optic nerve damage caused by high intraocular pressure (IOP).

37. The method of claim 36 , wherein the disorder is glaucoma.

38. The method of claim 36 , wherein the disorder is related to an increase in intraocular pressure (TOP).

39. The method of claim 36 , wherein the disorder is optic nerve damage caused by high intraocular pressure (IOP).

40. The method of claim 36 , wherein the host is a human.

41. The method of claim 36 , wherein the compound is administered via intravitreal, intrastromal, intracameral, sub-tenon, sub-retinal, retro-bulbar, peribulbar, suprachoroidal, choroidal, subchoroidal, conjunctival, subconjunctival, episcleral, posterior juxtascleral, circumcorneal, or tear duct injection.

42. The method of claim 41 , wherein the compound is administered via intravitreal injection.

43. A method for the treatment of an ocular disorder treatable with a beta-blocker comprising administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of claim 24 to a host in need thereof wherein the disorder is selected from glaucoma, age-related macular degeneration (AMD), a disorder related to an increase in intraocular pressure (TOP), a disorder related to neuroprotection, diabetic retinopathy, and optic nerve damage caused by high intraocular pressure (TOP).

44. The method of claim 43 , wherein the disorder is glaucoma.

45. The method of claim 43 , wherein the disorder is related to an increase in intraocular pressure (TOP).

46. The method of claim 43 , wherein the disorder is optic nerve damage caused by high intraocular pressure (IOP).

47. The method of claim 43 , wherein the host is a human.

48. The method of claim 43 , wherein the compound is administered via intravitreal, intrastromal, intracameral, sub-tenon, sub-retinal, retro-bulbar, peribulbar, suprachoroidal, choroidal, subchoroidal, conjunctival, subconjunctival, episcleral, posterior juxtascleral, circumcorneal, or tear duct injection.

49. The method of claim 48 , wherein the compound is administered via intravitreal injection.