Novel benzopyran analogs and their use for the treatment of glaucoma

• US 20050209314A1
• Filed: 05/06/2005
• Published: 09/22/2005
• Est. Priority Date: 12/13/2002
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Alcon Incorporated
• Inventors: Hellberg, Mark R., Namil, Abdelmoula
• Granted Patent: US 7,396,856 B2
• Time in Patent Office: Days
• US Class Current: 514/456
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: C07D 311/76 Benzo[c]pyrans

Abstract

Novel benzopyran analogs are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the present invention.

Claims

1. A method for the treatment of glaucoma comprising administering to a patient a pharmaceutically effective amount of a composition comprising at least one compound of Formula I:

2. The method of claim 1, wherein

R¹ and R² are hydrogens

R³ is C_1-3alkyl,

R⁵ is chosen from hydrogen, F or OR⁷;

and

R⁷ is C_1-3alkyl.

3. The method of claim 1, wherein said compound is selected from a group consisting of:

(+/−

) 2-(5, S-Dimethoxy-isochromaii-7-yl)-1-methyl-ethylamine

(+) 2-(5,8-Dimetlhoxy-isochroman-7-yl)-1-methyl-etlhylamine

(−

)-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethyl amine

2-(5,8-Dimethoxy-isochroman-7-yl)-2-hydroxy-1-methyl-ethylamine

2-(5,8-Dimethoxy-isochroman-7-yl)-2-methoxy-1-methyl-ethylamine

2-(8-Fluoro-5-methoxy-isochroman-7-yl)-1-methyl-ethylamine

2-(5,8-Dimethoxy-isochroman-7-yl)-11,2-dimethyl-ethylamine

and pharmaceutically acceptable salts and solvates thereof.

4. A method of controlling normal or elevated intraocular pressure comprising administering to a patient a pharmaceutically effective amount of a composition comprising at least one compound of Formula I:

5. The method of claim 4, wherein

R¹ and R² are hydrogens

R³ is C_1-3alkyl,

R⁵ is chosen from hydrogen, F or OR¹;

and

R⁷ is C_1-3alkyl.

6. The method of claim 4, wherein said compound is selected from a group consisting of:

(+/−

) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

(+) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

(−

) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-2-hydroxy-1-methyl-ethyl amine;

2-(5,8-Dimethoxy-isochroman-7-yl)-2-methoxy-1-methyl-ethylamine;

2-(8-Fluorb-5-methoxy-isochroman-7-yl)-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-1,2-dimethyl-ethylamine;

and pharmaceutically acceptable salts and solvates thereof.

7. A method of binding or activating serotonin receptors in a mammal, comprising administering to the mammal an effective amount of a composition comprising at least one compound of Formula I:

8. The method of claim 7, wherein

R¹ and R² are hydrogens;

R³ is C_1-3alkyl;

R⁵ is chosen from hydrogen, F or OR⁷; and

R⁷ is C_1-6alkyl.

9. The method of claim 7, wherein said compound is selected from a group consisting of:

(+/−

) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

(+) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

(−

) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-2-hydroxy-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-2-methoxy-1-methyl-ethylamine;

2-(8-Fluoro-5-methoxy-isochroman-7-yl)-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-1,2-dimethyl-ethyl amine;

and pharmaceutically acceptable salts and solvates thereof.

10. A compound represented by Formula I:

11. The compound of claim 10, wherein said compound is selected from the group consisting of

(+/−

) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

(+) 2-(5,8-Dimethoxy-isochiroman-7-yl)-1-methyl-ethylamine;

(−

) 2-(5,8-Dimethoxy-isochroman-7-yl)-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-2-hydroxy-1-methyl-ethylamine;

2-(5,8-Dimethoxy-isochroman-7-yl)-2-methoxy-1-methyl-ethylamine;

2-(8-Fluoro-5-methoxy-isochroman-7-yl)-1-methyl-ethylamine; and

2-(5,8-Dimethoxy-isochroman-7-yl)-1,2-dimethyl-ethylamine;

12. A pharmaceutical composition comprising the compound of claim 10 and at least one vehicle.