Oxazolyl-methylether derivatives as ALX receptor agonists
View Patent ↗The invention relates to oxazolyl-methylether derivatives of formula (I), wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description, their preparation and their use as pharmaceutically active compounds.
1. A compound of the formula (I),
wherein
R 1 represents phenyl which is unsubstituted or mono-substituted with halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 2 )fluoroalkyl or (C 1 -C 2 )fluoroalkoxy;
R 2 represents hydrogen, methyl or cyclopropyl;
R 3 and R 4 are identical and represent hydrogen or methyl; and
R 5 represents (C 1 -C 2 )alkyl; or a salt thereof.
2. The compound according to claim 1 , wherein
R 1 represents phenyl which is unsubstituted or mono-substituted with fluoro, chloro, methyl, methoxy, trifluoromethyl or trifluoromethoxy;
R 2 represents hydrogen or methyl;
R 3 and R 4 are identical and represent hydrogen or methyl; and
R 5 represents methyl; or a salt thereof.
3. The compound according to claim 1 , wherein
R 1 represents phenyl which is unsubstituted or mono-substituted with fluoro, chloro, methyl, methoxy, trifluoromethyl or trifluoromethoxy; or a salt thereof.
4. The compound according to claim 1 , wherein when R 1 represents a mono-substituted phenyl group, said phenyl group is substituted in meta-position; or a salt thereof.
5. The compound according to claim 1 , wherein R 2 represents hydrogen or methyl; or a salt thereof.
6. The compound according to claim 1 , wherein R 2 represents methyl; or a salt thereof.
7. The compound according to claim 1 , wherein R 3 and R 4 both represent hydrogen; or a salt thereof.
8. The compound according claim 1 , wherein R 3 and R 4 both represent methyl; or a salt thereof.
9. The compound according claim 1 , wherein R 5 represents methyl; or a salt thereof.
10. The compound according to claim 1 , wherein the compound is:
N-(2-((4-(2-methoxypropan-2-yl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(m-tolyl)oxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(m-tolyl)oxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-phenyloxazole-4-carboxamide;
5-(3-chlorophenyl)-N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyloxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide;
5-(3-chlorophenyl)-N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)oxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-5-(3-methoxyphenyl)oxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-5-(3-methoxyphenyl)-2-methyloxazole-4-carboxamide;
5-(3-fluorophenyl)-N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyloxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide;
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide;
2-cyclopropyl-N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide; or
N-(2-((4-(methoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-5-phenyloxazole-4-carboxamide; or a salt thereof.
11. The compound according to claim 1 , wherein the compound is:
N-(2-((4-(ethoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(m-tolyl)oxazole-4-carboxamide; or
N-(2-((4-(ethoxymethyl)oxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-5-phenyloxazole-4-carboxamide; or a salt thereof.
12. A medicament comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising, as active principle, a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.
14. A method of treating a disease or condition comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1 , wherein the disease is inflammation mediated by the lipoxin A4 receptor pathway.
15. A method of treating a disease or condition comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 10 , wherein the disease is inflammation mediated by the lipoxin A4 receptor pathway.
16. A method of treating a disease or condition comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1 , wherein the disease is Alzheimer's disease mediated by the lipoxin A4 receptor pathway.
17. A method of treating a disease or condition comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 10 , wherein the disease is Alzheimer's disease mediated by the lipoxin A4 receptor pathway.