Combination therapy

Patent metadata

Field	Value
Publication number	US-9849122-B2
Application number	US-201615142461-A
Country	US
Kind code	B2
Filing date	Apr 29, 2016
Priority date	Mar 15, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Aerie Pharmaceuticals Inc

Inventors

• Kopczynski Casey
• Lin Cheng-Wen
• Sturdivant Jill Marie
• Delong Mitchell A

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K31/557

  Eicosanoids, e.g. leukotrienes {or prostaglandins} · CPC title

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title