Compounds and compositions for the treatment of ocular disorders
View Patent ↗The disclosure describes prodrugs and derivatives of prostaglandins, carbonic anhydrase inhibitors, kinase inhibitors, beta-adrenergic receptor antagonists and other drugs, as well as controlled delivery formulations containing such prodrugs and derivatives, for the treatment of ocular disorders.
1. A compound of Formula XV:
or a pharmaceutically acceptable salt thereof;
wherein:
R 32 is R 35 ;
R 35 is selected from
R 51 is
R 15 is R 17 ;
R 17 is selected from H and —C(O)A;
A is selected from H, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkyloxy, and alkyloxy; and
x and y are independently selected from an integer between 1 and 30.
2. The compound of claim 1 , wherein x and y are independently selected from 1, 2, 3, 4, 5, and 6.
3. The compound of claim 2 , wherein x is 1 and y is selected from 1, 2, 3, and 4.
4. The compound of claim 2 , wherein x is 2 and y is selected from 1, 2, 3, and 4.
5. The compound of claim 3 , wherein x is 1 and y is 3.
6. The compound of claim 3 , wherein x is 1 and y is 4.
7. The compound of claim 1 , wherein R 15 is hydrogen.
8. The compound of claim 1 , wherein R 35 is
9. The compound of claim 8 , wherein R 15 is hydrogen.
10. The compound of claim 9 , wherein x and y are independently selected from 1, 2, 3, and 4.
11. The compound of claim 10 , wherein x is 1 or 2 and y is selected from 2, 3, and 4.
12. The compound of claim 11 , wherein x is 2 and y is 3.
13. The compound of claim 11 , wherein x is 2 and y is 4.
14. The compound of claim 11 , wherein x is 1 and y is 3.
15. The compound of claim 11 , wherein x is 1 and y is 4.
16. The compound of claim 1 , wherein R 35 is
17. The compound of claim 16 , wherein R 15 is hydrogen.
18. The compound of claim 17 , wherein x and y are independently selected from 1, 2, 3, and 4.
19. The compound of claim 18 , wherein x is 1 or 2 and y is selected from 2, 3, and 4.
20. The compound of claim 19 , wherein x is 2 and y is 3.
21. The compound of claim 19 , wherein x is 2 and y is 4.
22. The compound of claim 19 , wherein x is 1 and y is 3.
23. The compound of claim 19 , wherein x is 1 and y is 4.
24. The compound of claim 1 of the formula
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 1 of the formula
or a pharmaceutically acceptable salt thereof.
26. The compound of claim 1 of the formula
or a pharmaceutically acceptable salt thereof.
27. The compound of formula
or a pharmaceutically acceptable salt thereof.
28. A pharmaceutical composition comprising a compound of claim 1 in a pharmaceutically acceptable carrier.
29. A pharmaceutical composition comprising a compound of claim 24 in a pharmaceutically acceptable carrier.
30. A pharmaceutical composition comprising a compound of claim 25 in a pharmaceutically acceptable carrier.
31. A pharmaceutical composition comprising a compound of claim 26 in a pharmaceutically acceptable carrier.
32. A pharmaceutical composition comprising a compound of claim 27 in a pharmaceutically acceptable carrier.
33. A method for the treatment of an ocular disorder treatable with both a tyrosine kinase inhibitor and a carbonic anhydrase inhibitor 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 (IOP), a disorder related to neuroprotection, or diabetic retinopathy.
34. The method of claim 33 , wherein the host is a human.
35. The method of claim 34 , wherein the disorder is optic nerve damage caused by high intraocular pressure (IOP).
36. The method of claim 34 , 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.
37. The method of claim 33 , wherein the compound is administered via intravitreal injection.
38. A method for the treatment of an ocular disorder treatable with both a tyrosine kinase inhibitor and a carbonic anhydrase inhibitor comprising administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of claim 27 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 (IOP), a disorder related to neuroprotection, or diabetic retinopathy.
39. The method of claim 38 , wherein the host is a human.
40. The method of claim 39 , wherein the disorder is optic nerve damage caused by high intraocular pressure (IOP).
41. The method of claim 39 , 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 38 , wherein the compound is administered via intravitreal injection.
43. The method according to claim 34 , wherein the disorder is glaucoma.
44. The method according to claim 34 , wherein the disorder is related to an increase in intraocular pressure (IOP).
45. The method according to claim 34 , wherein the disorder is related to neuroprotection.
46. The method according to claim 39 , wherein the disorder is glaucoma.
47. The method according to claim 39 , wherein the disorder is related to an increase in intraocular pressure (IOP).
48. The method according to claim 39 , wherein the disorder is related to neuroprotection.