IMIDAZOLE COMPOUNDS AS EAAT3 INHIBITORS

• US 20190233379A1
• Filed: 04/12/2019
• Published: 08/01/2019
• Est. Priority Date: 10/14/2016
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: HOENER, Marius, WICHMANN, Juergen
• Granted Patent: US 10,556,870 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07D 233/58 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

Abstract

The invention provides novel compounds having the general formula (I)

wherein R¹, R¹′, R², R³, R⁴ are as defined herein, compositions including the compounds and methods of using the compounds.

Claims

1. A compound of formula (I):

2. A compound according to claim 1, wherein R¹ is methyl.

3. A compound according to claim 1, wherein

R² is selected from the group consisting of

i) methyl,

ii) ethyl,

iii) isopropyl, and

iv) tert-butyl.

4. A compound according to claim 1, wherein

R³ is selected from the group consisting of

i) chloro,

ii) fluoro, and

iii) trifluoromethyl.

5. A compound according to claim 1, wherein

R⁴ is H.

6. A compound according to claim 1, wherein

R¹′

and R¹ are both methyl;

R² is selected from the group consisting of

i) methyl,

ii) ethyl,

iii) isopropyl, and

iv) tert-butyl;

R³ is selected from the group consisting of

i) chloro,

ii) fluoro, and

iii) trifluoromethyl; and

R⁴ is H;

or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 1, selected from the group consisting of:

N-tert-butyl-3-(4-fluorophenyl)-5-(3-propan-2-ylimidazol-4-yl)benzamide;

N-tert-butyl-3-(3-propan-2-ylimidazol-4-yl)-5-[4-(trifluoromethyl)phenyl]benzamide;

N-tert-butyl-3-(4-chlorophenyl)-5-(3-propan-2-ylimidazol-4-yl)benzamide;

N-tert-butyl-3-(4-chlorophenyl)-5-(3-methylimidazol-4-yl)benzamide;

N-tert-butyl-3-(3-methylimidazol-4-yl)-5-[4-(trifluoromethyl)phenyl]benzamide;

N-tert-butyl-3-(4-fluorophenyl)-5-(3-methylimidazol-4-yl)benzamide;

N-tert-butyl-3-(3-tert-butylimidazol-4-yl)-5-(4-chlorophenyl)benzamide;

N-tert-butyl-3-(4-chlorophenyl)-5-(3-ethylimidazol-4-yl)benzamide;

N-tert-butyl-3-(3-ethylimidazol-4-yl)-5-(4-fluorophenyl)benzamide;

N-tert-butyl-3-(3-ethylimidazol-4-yl)-5-[4-(trifluoromethyl)phenyl]benzamide;

N-tert-butyl-3-(3-tert-butylimidazol-4-yl)-5-(4-fluorophenyl)benzamide;

N-tert-butyl-3-(3-tert-butylimidazol-4-yl)-5-[4-(trifluoromethyl)phenyl]benzamide;

or a pharmaceutically acceptable salt thereof.

8. A process to prepare a compound according to claim 1 comprising

a) the reaction of a compound of formula (II) in the presence of a compound of formula (III), wherein R¹, R¹′

, R², R³ and R⁴ are as defined in claim 1;

10. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

14. A method for the treatment or prophylaxis of an ocular condition, which method comprises administering an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

9. (canceled)

11. (canceled)

12. (canceled)

13. (canceled)

15. (canceled)

16. (canceled)