Fluorinated bridged spiro[2.4]heptane derivatives as ALX receptor agonists

1. A compound of formula (I)

wherein

n represents 1 or 2; and

R 1 represents hydrogen or fluoro;

or a salt thereof.

2. The compound according to claim 1 , wherein n represents 1; or a salt thereof.

3. The compound according to claim 1 , wherein n represents 2; or a salt thereof.

4. The compound according to claim 1 , wherein R 1 represents hydrogen; or a salt thereof.

5. The compound according to claim 1 , wherein R 1 represents fluoro; or a salt thereof.

6. The compound according to claim 1 , wherein R 1 represents hydrogen and the two stereogenic centers at the heterocyclyl group, which is attached to the amide nitrogen-atom, are relative to each other in trans-configuration;

or a salt thereof.

7. The compound according to claim 1 , wherein said compound is:

(1 S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3 S,4S)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;

(1 S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-((3R,4R)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;

(1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-(cis-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;

(1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-(3,3-difluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;

(1S,2R,3R,4R)—N2-(4-Bromo-2-fluorobenzyl)-N3-(cis-4-fluoropyrrolidin-3-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide; or

(1 S,2R,3R,4R)—N2-(4-Bromo-2-fluorobenzyl)-N3-(trans-4-fluoropyrrolidin-3-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;

or a salt thereof.

8. The compound according to claim 1 , wherein the compound is: (1 S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-((3S,4S)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide; or a salt thereof.

9. The compound according to claim 1 , wherein the compound is: (1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-((3R,4R)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide; or a salt thereof.

10. The compound according to claim 1 , wherein the compound is: (1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-(cis-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide; or a salt thereof.

11. The compound according to claim 1 , wherein the compound is: (1S,2R,3R,4R)—N2-(4-Bromo-2-fluorobenzyl)-N3-(trans-4-fluoropyrrolidin-3-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide; or a salt thereof.

12. A medicament comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising, as active principle, a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

14. A method of treating a disease comprising administering to a subject in need thereof a compound according to claim 1 , wherein the disease is inflammatory diseases, obstructive airway diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases or amyloid-mediated disorders.

15. A method of treating a disease comprising administering to a subject in need thereof a pharmaceutical composition according to claim 13 , wherein the disease is inflammatory diseases, obstructive airway diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases or amyloid-mediated disorders.

16. A method of modulating an immune response comprising administering to a subject in need thereof a compound according to claim 1 .

17. A method of modulating an immune response comprising administering to a subject in need thereof a pharmaceutical composition according to claim 13 .