Substituted arylamide oxazepinopyrimidone derivatives

1. A compound of formula (I):

wherein:

Y represents two hydrogen atoms, a sulphur atom, an oxygen atom, or a C 1-2 alkyl group and a hydrogen atom;

Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C 1-3 alkyl group, a sulphur atom, a methylene group optionally substituted by one or two groups chosen from a C 1-6 alkyl group, a hydroxyl group, a C 1-6 alkoxy group, a C 1-2 perhalogenated alkyl group or an amino group;

R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom;

R2 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;

R3 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxyl group, a C 1-6 alkoxy group, a C 1-2 perhalogenated alkoxy group, a C 1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C 1-6 monoalkylamino group, a C 2-12 dialkylamino group, an acetoxy group, an aminosulfonyl group, a 4-15 membered heterocyclic group, this group being optionally substituted by a C 1-6 alkyl group, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxyl group, or a C 1-6 alkoxy group;

R4 represents a hydrogen atom or a C 1-6 alkyl group; and

n represents 0 to 3;

or a salt thereof.

2. The compound according to claim 1 , wherein:

Y represents an oxygen atom or two hydrogen atoms;

z represents a bond;

R1 represents an unsubstituted 4-pyridine ring or unsubstituted 4-pyrimidine ring;

R2 represents an hydrogen atom;

R3 represents a benzene group optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a halogen atom, a C 1-6 alkoxy group, an hydroxy group, an amino group, a OC(O)(C 1-6 -alkyl) group, an aminosulfonyl group, and an oxadiazole group, the oxadiazole group being optionally substituted by C 1-6 alkyl group, a halogen atom, or a C 1-6 alkoxy group;

R4 represents an hydrogen atom; and n represents 0;

or a salt thereof.

3. The compound according to claim 1 which is selected from the group consisting of:

(+/−)-4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(−)-4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+)-4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-4-Amino-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-5-sulfamoyl-benzamide;

(+/−)-2,4-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-2,3-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-2,5-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-5-Bromo-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-Acetic acid 2-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-ylcarbamoyl)-phenyl ester;

(+/−)-2-Methoxy-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-2-Hydroxy-N-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-9-Benzylamino-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa -1,4a-diaza-benzocyclohepten-4-one;

(+/−)-4-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-5-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4a-diaza-benzocyclohepten-9-yl)-benzamide;

(+/−)-9-(2-Methoxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one;

(+/−)-9-(4-Fluoro-2-methoxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one;

(+/−)-9-(5-Fluoro-2-methoxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one;

(+/−)-9-(5-Chloro-2-hydroxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one;

(+/−)-9-(5-Chloro-2-methoxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one;

(+/−)-9-(5-Bromo-2-methoxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one; and

(+/−)-9-(2,5-Dimethoxy-benzylamino)-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one;

or a salt thereof, or a solvate thereof or a hydrate thereof.

4. A compound represented by formula (III), (VI) or (VII):

wherein R1 and R2 are as defined for the compound of formula (I) according to claim 1 .

5. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutical additives.

6. A pharmaceutical composition comprising a compound of formula (I) according to claim 2 or a pharmaceutically acceptable salt thereof and one or more pharmaceutical additives.

7. A pharmaceutical composition comprising a compound of formula (I) according to claim 3 or a pharmaceutically acceptable salt thereof and one or more pharmaceutical additives.

8. A method of treating a neurodegenerative disease in a patient comprising administering to said patient a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, wherein said neurodegenerative disease is selected from the group consisting of Alzheimer's disease, Parkinson's disease, tauopathies, vascular dementia; acute stroke, traumatic injuries; cerebrovascular accidents, brain cord trauma, spinal cord trauma;

peripheral neuropathies; retinopathies and glaucoma.

9. A method of treating a disease in a patient, said disease selected from the group consisting of non-insulin dependent diabetes; obesity; manic depressive illness; schizophrenia; and cancers; wherein said cancer is selected from the group consisting of breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia or virus-induced tumors; comprising administering to said patient a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof.

10. A method of treating malaria in a patient, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof.

11. A method of treating Pemphigus vulgaris in a patient, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof.

12. A process for the preparation of a compound of formula (I) according to claim 1 comprising:

reacting a compound of formula (III):

with a compound of formula (II):

wherein z, R1, R2, R3, Y and n are as defined in claim 1 , and L represents a leaving group.