Hydroxylated aminotriazole derivatives as ALX receptor agonists
View Patent ↗The invention relates to hydroxylated aminotriazole derivatives of formula (I), wherein Q, R 1 , R 2 , R 3 and R 4 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 both represent methyl; or R 3 and R 4 form, together with the carbon atom to which they are attached, a cyclopropyl ring; and
Q represents O, or S;
or a salt thereof.
2. The compound according to claim 1 , 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 or methyl;
R 3 and R 4 both represent methyl; or R 3 and R 4 form, together with the carbon atom to which they are attached, a cyclopropyl ring; and
Q represents O;
or a salt thereof.
3. The compound according to claim 1 , wherein
R 1 represents phenyl which is unsubstituted or mono-substituted with halogen, (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy;
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 3 and R 4 both represent methyl;
or a salt thereof.
7. The compound according to claim 1 , wherein R 3 and R 4 form, together with the carbon atom to which they are attached, a cyclopropyl ring;
or a salt thereof.
8. The compound according to claim 1 , wherein Q represents O;
or a salt thereof.
9. The compound according to claim 1 , wherein the compound is:
2-Methyl-5-m-tolyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
2-Methyl-5-m-tolyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-cyclopropyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-Phenyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(4-Fluoro-phenyl)-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
2-Methyl-5-(3-trifluoromethyl-phenyl)-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(3-Methoxy-phenyl)-2-methyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(3-Chloro-phenyl)-2-methyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(3-Chloro-phenyl)-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(3-Methoxy-phenyl)-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
2-Methyl-5-phenyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(3-Fluoro-phenyl)-thiazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
2-Methyl-5-(3-trifluoromethoxy-phenyl)-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-(3-Fluoro-phenyl)-2-methyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
5-m-Tolyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide; or
2-Cyclopropyl-5-m-tolyl-oxazole-4-carboxylic acid {2-[4-(1-hydroxy-1-methyl-ethyl)-oxazol-2-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide;
or a salt thereof.
10. A medicament comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
11. A pharmaceutical composition comprising, as an active principle, a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.
12. 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 or condition is responsive to an ALX receptor agonist; and wherein the disease is an inflammatory disease, obstructive airway disease, allergic condition, HIV-mediated retroviral infection, cardiovascular disorder, neuroinflammation, neurological disorder, pain, prion-mediated disease or amyloid-mediated disorder or wherein the condition is the modulation of immune responses.
13. 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 9 , wherein the disease or condition is responsive to an ALX receptor agonist; and wherein the disease is an inflammatory disease, obstructive airway disease, allergic condition, HIV-mediated retroviral infection, cardiovascular disorder, neuroinflammation, neurological disorder, pain, prion-mediated disease or amyloid-mediated disorder or wherein the condition is the modulation of immune responses.