Combination therapy
Described herein are compounds and compositions for treating glaucoma and/or reducing intraocular pressure. Compositions may comprise an isoquinoline compound and a prostaglandin or a prostaglandin analog. Compounds described herein include those in which an isoquinoline compound is covalently linked to a prostaglandin or a prostaglandin analog, and those in which an isoquinoline compound and a prostaglandin free acid together form a salt.
1. A compound according to formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
Y is phenylene;
B is —NR 1 R 2 or —CH 2 NR 1 R 2 ;
R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl;
X 1 and X 2 are hydrogen; and
PG is an acyl radical of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, unoprostone, or PGF 2α .
2. The compound of claim 1 , wherein:
B is —CH 2 NR 1 R 2 ; and
R 1 and R 2 are hydrogen.
3. The compound of claim 1 , wherein
PG is an acyl radical of latanoprost.
4. The compound of claim 1 , wherein PG is an acyl radical of AR-102.
5. The compound of claim 1 , wherein PG is an acyl radical of bimatoprost.
6. A composition comprising a compound of claim 1 , and at least one of a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar or a sugar alcohol, or a surfactant.
7. The compound of claim 1 , wherein PG is an acyl radical of travoprost.
8. A method of treating glaucoma in a subject in need thereof, comprising administering to the subject a compound of claim 1 .
9. The method of claim 8 , wherein the compound is administered topically to an eye of the subject.
10. A method of reducing intraocular pressure in a subject in need thereof, comprising topically administering to an eye of the subject a compound of claim 1 .
11. A compound, wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12. A composition comprising a compound of claim 11 , further comprising at least one of a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar or a sugar alcohol, or a surfactant.
13. A method of treating glaucoma in a subject in need thereof, comprising administering to the subject a compound of claim 11 .
14. The method of claim 13 , wherein the compound is administered topically to an eye of the subject.
15. A method of reducing intraocular pressure in a subject in need thereof, comprising topically administering to an eye of the subject a compound of claim 11 .
16. A compound according to formula (II):
or a pharmaceutically acceptable salt thereof;
wherein
Y is phenylene;
B is —CH 2 NR 1 R 2 ;
R 1 and R 2 are hydrogen;
X 1 and X 2 are hydrogen; and
PG is an acyl radical of latanoprost.
17. A composition comprising a compound of claim 16 , further comprising at least one of a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar or a sugar alcohol, or a surfactant.
18. A method of treating glaucoma in a subject in need thereof, comprising administering to the subject a compound of claim 16 .
19. The method of claim 18 , wherein the compound is administered topically to an eye of the subject.
20. A method of reducing intraocular pressure in a subject in need thereof, comprising topically administering to an eye of the subject a compound of claim 16 .
21. The compound of claim 2 , wherein PG is an acyl radical of bimatoprost.