Resolvin analogs compounds, methods and uses thereof
The present application relates to resolvin analogs having anti-inflammatory and antioxidant properties, uses and methods using the same. More specifically, the present application relates to compounds of formula (I) or an enantiomer, isomer, salt or solvate thereof.
1. A compound of Formula (I):
wherein
R 1 is selected from the group consisting of H and C 1-8 alkyl;
R 2 , R 3 and R 4 are independently selected from the group consisting of H, C 1-8 alkyl, and a suitable protecting group; wherein R 2 and R 3 may be joined to form, together with the atom therebetween, an heterocyclyl group;
R 5 and R 6 are independently selected from the group consisting of H and C 1-8 alkyl;
R 7 is selected from the group consisting of linear or branched C 1-10 alkyl and linear or branched C 2-10 alkenyl, wherein the alkyl and alkenyl may be interrupted by 1 to 3 heteroatoms selected from O, N and S, and may be substituted with one or more group selected from halogen, —OH, —CF 3 , —CN, —NH 2 , —SH and phenyl,
is absent or represents a bond,
wherein R 4 is absent when is a bond,
or an enantiomer, isomer, salt or solvate thereof.
2. A compound of Formula (IA):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and are as defined in claim 1 , and n and m are independently an integer from 0 to 7,
or an enantiomer, isomer, salt or solvate thereof.
3. The compound of claim 1 , wherein R 7 is pentyl, propyl, octyl or benzyl.
4. The compound of claim 1 , wherein R 1 is H, methyl, ethyl or propyl.
5. The compound of claim 1 , wherein R 1 is H or methyl.
6. The compound of claim 1 , wherein R 2 , R 3 and R 4 are independently selected from the group consisting of H, methyl, ethyl, and propyl.
7. The compound of claim 1 , wherein R 2 and R 3 are joined to form, together with the atom therebetween, an acetal group.
8. The compound of claim 1 , wherein R 2 , R 3 and R 4 are each H.
9. The compound of claim 1 , wherein R 5 and R 6 are each H, methyl or ethyl.
10. The compound of claim 1 , wherein R 5 and R 6 are each methyl.
11. The compound of claim 1 having the structure of Formula (I-2):
or an enantiomer, isomer, salt or solvate thereof.
12. The compound of claim 1 having the structure of Formula (I-1):
or an enantiomer, isomer, salt or solvate thereof.
13. The compound of claim 1 having the structure of Formula (IB)
or an enantiomer, isomer, salt or solvate thereof.
14. The compound of claim 1 having the structure of Formula (IC)
or an enantiomer, isomer, salt or solvate thereof.
15. A pharmaceutical composition comprising a compound as defined in claim 1 , or an enantiomer, isomer, salt or solvate thereof, and a pharmaceutically acceptable excipient, diluent or carrier.
16. A pharmaceutical composition comprising a compound as defined in claim 11 , or an enantiomer, isomer, salt or solvate thereof, and a pharmaceutically acceptable excipient, diluent or carrier.
17. A pharmaceutical composition comprising a compound as defined in claim 12 , or an enantiomer, isomer, salt or solvate thereof, and a pharmaceutically acceptable excipient, diluent or carrier.
18. A pharmaceutical composition comprising a compound as defined in claim 13 , or an enantiomer, isomer, salt or solvate thereof, and a pharmaceutically acceptable excipient, diluent or carrier.
19. A pharmaceutical composition comprising a compound as defined in claim 14 , or an enantiomer, isomer, salt or solvate thereof, and a pharmaceutically acceptable excipient, diluent or carrier.
20. A method for treating an inflammatory disease or disorder, comprising administering an effective amount of a compound as defined in claim 1 in a subject in need thereof.
21. The method of claim 20 , wherein the inflammatory disease or disorder is selected from arthritis, osteoarthritis, inflammatory bowel disease or disorder, and skin inflammatory disease and disorder.
22. A method for inhibiting monocytes/macrophages differentiation, comprising administering an effective amount of a compound as defined in claim 1 in a subject in need thereof.
23. A method for inhibiting osteoclasts recruitment, comprising administering an effective amount of a compound as defined in claim 1 in a subject in need thereof.
24. A method for inhibiting MMP-13 production, comprising administering an effective amount of a compound as defined in claim 1 in a subject in need thereof.
25. A method for inhibiting ultraviolet-induced hyaluronic acid degradation, comprising administering an effective amount of a compound as defined in claim 1 in a subject in need thereof.
26. A method for inhibiting COX-2 expression, comprising administering an effective amount of a compound as defined in claim 1 in a subject in need thereof.