SIK inhibitor for use in a method of treating an inflammatory and/or immune disorder
The present invention relates to the discovery that salt inducible kinases (SIKs) suppress the formation of anti-inflammatory molecules such as IL-10, which are important for the resolution of inflammation and identifies SIK inhibitors that may be used to treat disorders associated with undesirable inflammation, such as inflammatory bowel disease and/or autoimmune disorders.
1. A compound of formula:
or a salt or solvate thereof.
2. The compound according to claim 1 , or a salt thereof.
3. A pharmaceutical formulation comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient.
4. A method of treating ulcerative colitis, wherein the method comprises administering a therapeutically effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt thereof, to a subject in need thereof:
wherein:
Ar 1 is a 5- or 6-membered, hetero- or homo-cyclic aromatic ring; wherein the 5- or 6-membered, hetero- or homo-cyclic aromatic ring is optionally substituted with C 1 -C 4 alkyl, saturated heterocyclic, -methylene-heterocyclic;
one instance of X is N, and the other instance of X is CH;
R 2 is
and
R 4 is hydrogen,
or
wherein R 5 is hydrogen or C 1 -C 4 alkyl.
5. The method according to claim 4 , wherein
Ar 1 is
and R 4 is
6. The method according to claim 4 , wherein the method comprises administering a therapeutically effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
7. The method according to claim 4 , wherein Ar 1 is a benzene ring; wherein the benzene ring is optionally substituted with C 1 -C 4 alkyl, saturated heterocyclic, or -methylene-heterocyclic.
8. The method according to claim 4 , wherein Ar 1 is a benzene ring substituted with saturated heterocyclic.
9. The method according to claim 4 , wherein Ar 1 is
10. The method according to claim 4 , wherein Ar 1 is
wherein X is 5- or 6-membered heterocyclyl comprising up to one oxygen atom in the heterocyclic ring system.
11. The method according to claim 4 , wherein Ar 1 is a 5- or 6-membered, heterocyclic aromatic ring; wherein the 5- or 6-membered, heterocyclic aromatic ring is optionally substituted with C 1 -C 4 alkyl, saturated heterocyclic, or -methylene-heterocyclic.
12. The method according to claim 4 , wherein Ar 1 is
13. The method according to claim 4 , wherein the method comprises administering a therapeutically effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
14. The method according to claim 4 , wherein the method comprises administering a therapeutically effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
15. The method according to claim 4 , wherein R 4 is
16. The method according to claim 4 , wherein R 4 is hydrogen or
17. The method according to claim 4 , wherein the compound, or pharmaceutically acceptable salt thereof, is administered in an encapsulated form.
18. The method according to claim 4 , wherein the compound, or pharmaceutically acceptable salt thereof, is administered in the form of a liposome.
19. The method according to claim 4 , wherein the therapeutically effective amount is effective for inhibiting a salt inducible kinase (SIK).
20. The method according to claim 4 , wherein the therapeutically effective amount is effective for increasing the formation of macrophages with a regulatory phenotype.